Trial Outcomes & Findings for A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen (NCT NCT00615056)

Last Updated: 2013-04-19

Results Overview

Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death").

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

171 participants

Primary outcome timeframe

Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks

Results posted on

2013-04-19

Participant Flow

Participant milestones

Participant milestones
Measure	Axitinib + FOLFIRI Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFOX Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Study STARTED	49	51	36	35
Overall Study Treated	46	51	36	35
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	49	51	36	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Axitinib + FOLFIRI Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFOX Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Study Death	31	31	21	23
Overall Study Lost to Follow-up	1	2	4	5
Overall Study Other	13	15	10	7
Overall Study Objective progression or relapse	0	2	0	0
Overall Study Withdrawal by Subject	0	1	1	0
Overall Study Discontinued by Sponsor	1	0	0	0
Overall Study Randomized but not treated	3	0	0	0

Baseline Characteristics

A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Axitinib + FOLFIRI n=49 Participants Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=51 Participants Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFOX n=36 Participants Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=35 Participants Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Total n=171 Participants Total of all reporting groups
Age, Customized 18 to 44 years	5 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	15 Participants n=21 Participants
Age, Customized 45 to 64 years	30 Participants n=5 Participants	34 Participants n=7 Participants	21 Participants n=5 Participants	22 Participants n=4 Participants	107 Participants n=21 Participants
Age, Customized Greater than and equal to 65 years	14 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	12 Participants n=4 Participants	49 Participants n=21 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	24 Participants n=7 Participants	20 Participants n=5 Participants	11 Participants n=4 Participants	73 Participants n=21 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	27 Participants n=7 Participants	16 Participants n=5 Participants	24 Participants n=4 Participants	98 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks

Population: Intent-to-treat (ITT) population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized.

Outcome measures

Outcome measures
Measure	Axitinib + FOLFOX n=36 Participants Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=35 Participants Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFIRI n=49 Participants Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=51 Participants Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Progression Free Survival (PFS)	7.59 Months Interval 5.62 to 11.07	6.44 Months Interval 5.52 to 13.11	5.72 Months Interval 4.5 to 7.42	6.87 Months Interval 4.96 to 9.13

SECONDARY outcome

Timeframe: Baseline until death or up to 1 year after the randomization of last participant

Population: ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug, or receive a different drug from that to which they were randomized.

Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

Outcome measures

Outcome measures
Measure	Axitinib + FOLFOX n=36 Participants Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=35 Participants Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFIRI n=49 Participants Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=51 Participants Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Overall Survival (OS)	17.1 Months Interval 10.1 to 23.0	14.1 Months Interval 9.0 to 16.4	12.9 Months Interval 10.2 to 16.6	15.7 Months Interval 12.1 to 23.0

SECONDARY outcome

Timeframe: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.

Outcome measures

Outcome measures
Measure	Axitinib + FOLFOX n=36 Participants Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=35 Participants Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFIRI n=49 Participants Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=51 Participants Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Percentage of Participants With Objective Response (OR)	19.4 Percentage of participants Interval 8.2 to 36.0	20.0 Percentage of participants Interval 8.4 to 36.9	24.5 Percentage of participants Interval 13.3 to 38.9	23.5 Percentage of participants Interval 12.8 to 37.5

SECONDARY outcome

Timeframe: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks

Population: DR was calculated for the subgroup of participants from the ITT set, with a confirmed objective tumor response (CR or PR).

Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

Outcome measures

Outcome measures
Measure	Axitinib + FOLFOX n=7 Participants Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=7 Participants Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFIRI n=12 Participants Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=12 Participants Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Duration of Response (DR)	10.15 Months Interval 4.17 to 12.91	10.94 Months Interval 4.53 to 12.68	7.52 Months Interval 5.22 to Upper limit of confidence interval was not estimable due to the large number of participants censored.	12.29 Months Interval 7.39 to 12.84

SECONDARY outcome

Timeframe: Baseline, Day 1 of cycles 2- 5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal

Population: ITT population. Here 'N' (number of participants analyzed) signifies participants evaluable for this measure and 'n' is number of participants analyzed at specific time point for each treatment arm respectively.

Symptom severity score is comprised of average of 14 MDASI-D core items (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, numbness or tingling and diarrhea) and ranges from 0 to 10. Participants were asked to rate severity of each symptom at their worst in last week; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Lower scores indicated better outcome. Total average score range: 0 to 10.

Outcome measures

Outcome measures
Measure	Axitinib + FOLFOX n=35 Participants Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=33 Participants Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFIRI n=39 Participants Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=46 Participants Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 9/Day 1 (n=19,26,19,17)	0.6 Units on a Scale Interval -0.1 to 1.3	0.8 Units on a Scale Interval 0.3 to 1.3	1.1 Units on a Scale Interval 0.3 to 1.9	-0.2 Units on a Scale Interval -0.7 to 0.2
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 19/Day 1 (n=6,10,9,5)	0.8 Units on a Scale Interval -0.2 to 1.8	1.4 Units on a Scale Interval 0.7 to 2.2	1.3 Units on a Scale Interval -1.5 to 4.1	0.5 Units on a Scale Interval -0.7 to 1.7
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 39/Day 1 (n=0,2,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	1.0 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale Interval -0.8 to 0.1
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 43/Day 1 (n=0,1,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	2.0 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 45/Day 1 (n=0,0,0,1 )	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	2.2 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 51/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 61/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.2 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 63/Day 1 (n=0,0,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 65/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 7/Day 1 (n=26,31,22,20)	0.6 Units on a Scale Interval 0.1 to 1.1	0.2 Units on a Scale Interval -0.5 to 0.9	0.7 Units on a Scale Interval 0.1 to 1.2	0.0 Units on a Scale Interval -0.6 to 0.5
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at end of treatment (n=21,29,27,22)	1.3 Units on a Scale Interval 0.4 to 2.1	0.9 Units on a Scale Interval 0.1 to 1.7	0.7 Units on a Scale Interval -0.2 to 1.6	0.5 Units on a Scale Interval -0.1 to 1.0
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 17/Day 1 (n=6,11,11,7)	0.9 Units on a Scale Interval 0.1 to 1.8	1.7 Units on a Scale Interval 0.7 to 2.7	2.0 Units on a Scale Interval -0.9 to 5.0	0.4 Units on a Scale Interval -0.3 to 1.0
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 11/Day 1 (n=15,24,16,15)	1.0 Units on a Scale Interval 0.2 to 1.8	0.1 Units on a Scale Interval -0.8 to 1.1	1.0 Units on a Scale Interval 0.1 to 1.9	0.1 Units on a Scale Interval -0.5 to 0.7
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 29/Day 1 (n=2,5,2,3)	-0.8 Units on a Scale Interval -1.7 to 0.1	0.9 Units on a Scale Interval -0.3 to 2.1	2.8 Units on a Scale Interval -25.8 to 31.4	-0.2 Units on a Scale Interval -1.3 to 0.9
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 13/Day 1 (n=13,19,15,10)	0.9 Units on a Scale Interval 0.2 to 1.6	0.8 Units on a Scale Interval 0.1 to 1.4	1.0 Units on a Scale Interval -0.5 to 2.6	0.1 Units on a Scale Interval -0.6 to 0.7
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 15/Day 1 (n=7,17,12,8)	0.5 Units on a Scale Interval -0.4 to 1.3	1.0 Units on a Scale Interval 0.4 to 1.6	0.8 Units on a Scale Interval -1.6 to 3.3	0.2 Units on a Scale Interval -0.3 to 0.7
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 31/Day 1 (n=1,5,2,2)	-0.3 Units on a Scale Interval -5.7 to 5.2	0.9 Units on a Scale Interval -1.4 to 3.2	4.9 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	-0.4 Units on a Scale Interval -1.2 to 0.3
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Baseline (n=39,46,35,33)	1.9 Units on a Scale Interval 1.3 to 2.5	2.0 Units on a Scale Interval 1.4 to 2.7	2.1 Units on a Scale Interval 1.6 to 2.6	1.8 Units on a Scale Interval 1.3 to 2.2
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 2/Day 1 (n=35, 39, 34,28)	0.7 Units on a Scale Interval 0.2 to 1.2	0.0 Units on a Scale Interval -0.4 to 0.5	0.6 Units on a Scale Interval 0.2 to 1.1	0.5 Units on a Scale Interval -0.1 to 1.0
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 3/Day 1 (n=36,36,33,26)	0.3 Units on a Scale Interval -0.4 to 1.0	0.2 Units on a Scale Interval -0.3 to 0.7	0.8 Units on a Scale Interval 0.2 to 1.4	0.2 Units on a Scale Interval -0.3 to 0.6
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 4/Day 1 (n=29,37,32,25)	0.5 Units on a Scale Interval -0.2 to 1.1	0.5 Units on a Scale Interval -0.1 to 1.1	0.8 Units on a Scale Interval 0.0 to 1.5	0.0 Units on a Scale Interval -0.4 to 0.5
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 5/Day 1 (n=28,29,24,24)	0.9 Units on a Scale Interval 0.2 to 1.7	0.4 Units on a Scale Interval -0.2 to 0.9	0.5 Units on a Scale Interval 0.0 to 1.1	0.1 Units on a Scale Interval -0.4 to 0.7
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 21/Day 1 (n=6,9,7,4)	0.9 Units on a Scale Interval -0.9 to 2.7	1.6 Units on a Scale Interval 0.3 to 2.8	1.1 Units on a Scale Interval -2.2 to 4.4	0.5 Units on a Scale Interval -0.5 to 1.5
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 33/Day 1 (n=1,3,2,1)	-0.8 Units on a Scale Interval -7.6 to 6.1	0.5 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	5.0 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	-0.6 Units on a Scale Interval -3.2 to 2.0
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 35/Day 1 (n=0,4,1,1)	0.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	2.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale Interval -1.5 to 0.7
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 37/Day 1 (n=0,4,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	1.0 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.5 Units on a Scale Interval -1.3 to 0.4
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 41/Day 1 (n=0,2,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	1.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale Interval -0.8 to 0.1
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 47/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 49/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.5 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 53/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 55/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 57/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 59/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 23/Day 1 (n=5,7,6,4)	0.4 Units on a Scale Interval -1.4 to 2.3	1.0 Units on a Scale Interval 0.8 to 1.2	2.6 Units on a Scale Interval 0.3 to 4.8	-0.3 Units on a Scale Interval -0.9 to 0.3
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 25/Day 1 (n=5,7,6,3)	0.2 Units on a Scale Interval -2.0 to 2.3	1.0 Units on a Scale Interval 0.5 to 1.4	2.2 Units on a Scale Interval -1.2 to 5.6	0.1 Units on a Scale Interval -1.2 to 1.4
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 27/Day 1 (n=2,7,3,3)	0.3 Units on a Scale Interval -5.4 to 5.9	1.1 Units on a Scale Interval 0.6 to 1.5	2.3 Units on a Scale Interval -20.8 to 25.5	0.4 Units on a Scale Interval -1.4 to 2.3

SECONDARY outcome

Timeframe: Baseline, Day 1 of cycle 2-5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal

Symptom Interference score is comprised of the average of 6 items on feeling or function from the MDASI-D core (general activity, mood, work, relations with others, walking, and enjoyment of life) and ranges from 0 to 10. Participants were asked to rate how much symptoms have interfered in last week; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Lower scores indicated better outcome. Total average score range: 0 to 10.

Outcome measures

Outcome measures
Measure	Axitinib + FOLFOX n=35 Participants Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=33 Participants Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFIRI n=39 Participants Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=46 Participants Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Baseline (n=39,46,35,33)	2.4 Units on a Scale Interval 1.6 to 3.2	2.8 Units on a Scale Interval 1.8 to 3.9	2.1 Units on a Scale Interval 1.4 to 2.8	1.7 Units on a Scale Interval 1.1 to 2.3
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 4/Day 1 (n=29,37,32,25)	0.2 Units on a Scale Interval -0.6 to 1.1	0.5 Units on a Scale Interval -0.2 to 1.3	0.8 Units on a Scale Interval -0.1 to 1.7	-0.2 Units on a Scale Interval -0.9 to 0.4
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 11/Day 1 (n=15,24,16,15)	0.8 Units on a Scale Interval 0.0 to 1.6	-0.2 Units on a Scale Interval -1.6 to 1.2	1.0 Units on a Scale Interval 0.0 to 2.1	0.3 Units on a Scale Interval -0.6 to 1.3
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 17/Day 1 (n=6,11,11,7)	0.7 Units on a Scale Interval -1.3 to 2.6	2.1 Units on a Scale Interval -0.1 to 4.3	2.4 Units on a Scale Interval 0.9 to 3.8	0.7 Units on a Scale Interval -0.7 to 2.1
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 21/Day 1 (n=6,9,7,4)	0.4 Units on a Scale Interval -1.0 to 1.8	2.1 Units on a Scale Interval 0.8 to 3.4	1.7 Units on a Scale Interval -0.3 to 3.7	1.0 Units on a Scale Interval -1.2 to 3.2
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 23/Day 1 (n=5,7,6,4)	0.9 Units on a Scale Interval -1.7 to 3.4	1.4 Units on a Scale Interval 0.8 to 2.0	2.2 Units on a Scale Interval 0.0 to 4.4	-0.3 Units on a Scale Interval -1.3 to 0.8
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 25/Day 1 (n=5,7,6,3)	-0.6 Units on a Scale Interval -2.7 to 1.5	1.4 Units on a Scale Interval 0.5 to 2.3	1.6 Units on a Scale Interval -0.9 to 4.1	0.5 Units on a Scale Interval -2.0 to 3.0
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 27/Day 1 (n=2,7,3,3)	-1.6 Units on a Scale Interval -5.7 to 2.4	1.3 Units on a Scale Interval 0.9 to 1.7	1.6 Units on a Scale Interval -16.4 to 19.6	0.9 Units on a Scale Interval -2.1 to 4.0
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 29/Day 1 (n=2,5,2,3)	-1.3 Units on a Scale Interval -15.0 to 12.5	1.3 Units on a Scale Interval -0.4 to 3.0	3.2 Units on a Scale Interval -26.5 to 32.8	0.0 Units on a Scale Interval -2.3 to 2.2
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 31/Day 1 (n=1,5,2,2)	-0.1 Units on a Scale Interval -26.6 to 26.4	1.2 Units on a Scale Interval -3.1 to 5.4	4.5 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	-0.5 Units on a Scale Interval -2.1 to 1.0
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 33/Day 1 (n=1,3,2,1)	-0.8 Units on a Scale Interval -29.3 to 27.8	0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	4.5 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	-0.2 Units on a Scale Interval -4.4 to 3.9
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 35/Day 1 (n=0,4,1,1 )	-1.2 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	3.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale Interval -1.9 to 1.2
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 37/Day 1 (n=0,4,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	1.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.4 Units on a Scale Interval -2.1 to 1.2
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 39/Day 1 (n=0,2,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	2.0 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale Interval -0.3 to -0.3
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 41/Day 1 (n=0,2,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	1.5 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.2 Units on a Scale Interval -2.3 to 2.0
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 43/Day 1 (n=0,1,0,1)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	1.8 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 45/Day 1 (n=0,0,0,1 )	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	2.5 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 47/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.2 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 49/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 51/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 53/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.2 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 55/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.3 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 57/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	0.0 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 59/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.2 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 61/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	0.0 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 63/Day 1 (n=0,0,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 65/Day 1 (n=0,1,0,0)	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	NA Units on a Scale Data was not analyzed as no participants were evaluable for the particular cycle.	-0.2 Units on a Scale 95% confidence interval was not estimable since only one participant was evaluable.
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at end of treatment (n=21,29,26,21)	1.5 Units on a Scale Interval 0.2 to 2.8	1.2 Units on a Scale Interval 0.0 to 2.4	1.3 Units on a Scale Interval 0.5 to 2.1	1.0 Units on a Scale Interval 0.3 to 1.6
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 2/Day 1 (n=35, 39, 34, 28)	0.1 Units on a Scale Interval -0.6 to 0.7	-0.5 Units on a Scale Interval -1.2 to 0.1	0.8 Units on a Scale Interval 0.0 to 1.5	0.9 Units on a Scale Interval 0.2 to 1.6
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 3/Day 1 (n=36,36,33,26)	0.3 Units on a Scale Interval -0.6 to 1.2	-0.2 Units on a Scale Interval -1.0 to 0.6	1.3 Units on a Scale Interval 0.5 to 2.2	0.3 Units on a Scale Interval -0.3 to 0.8
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 5/Day 1 (n=28,29,24,24)	0.8 Units on a Scale Interval -0.4 to 2.0	0.3 Units on a Scale Interval -0.6 to 1.2	1.0 Units on a Scale Interval 0.3 to 1.6	0.4 Units on a Scale Interval -0.7 to 1.4
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 7/Day 1 (n=26,30,22,20)	0.4 Units on a Scale Interval -0.3 to 1.1	0.0 Units on a Scale Interval -0.8 to 0.7	0.7 Units on a Scale Interval -0.1 to 1.5	0.4 Units on a Scale Interval -0.4 to 1.2
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 9/Day 1 (n=18,25,19,17)	0.6 Units on a Scale Interval -0.5 to 1.6	0.3 Units on a Scale Interval -0.8 to 1.4	1.1 Units on a Scale Interval 0.2 to 1.9	0.3 Units on a Scale Interval -0.6 to 1.1
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 13/Day 1 (n=13,19,15,10)	1.3 Units on a Scale Interval 0.4 to 2.2	0.7 Units on a Scale Interval -0.7 to 2.1	1.1 Units on a Scale Interval -0.4 to 2.7	0.7 Units on a Scale Interval -0.2 to 1.5
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 15/Day 1 (n=7,17,12,8)	-0.1 Units on a Scale Interval -1.4 to 1.3	1.3 Units on a Scale Interval 0.0 to 2.5	2.3 Units on a Scale Interval 0.8 to 3.8	0.9 Units on a Scale Interval -0.3 to 2.0
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal Change at Cycle 19/Day 1 (n=6,10,9,5)	0.3 Units on a Scale Interval -1.6 to 2.2	2.4 Units on a Scale Interval 1.2 to 3.7	2.1 Units on a Scale Interval 0.6 to 3.6	0.8 Units on a Scale Interval -0.6 to 2.3

Adverse Events

Axitinib + FOLFIRI

Serious events: 17 serious events

Other events: 45 other events

Deaths: 0 deaths

Bevacizumab + FOLFIRI

Serious events: 9 serious events

Other events: 51 other events

Deaths: 0 deaths

Axitinib + FOLFOX

Serious events: 11 serious events

Other events: 35 other events

Deaths: 0 deaths

Bevacizumab + FOLFOX

Serious events: 5 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Axitinib + FOLFIRI n=46 participants at risk Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=51 participants at risk Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFOX n=36 participants at risk Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=35 participants at risk Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
General disorders General physical health deterioration	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Disease progression	4.3% 2/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.9% 3/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hyperbilirubinaemia	4.3% 2/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic mass	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis pharyngeal	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Febrile neutropenia	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Otosalpingitis	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	4.3% 2/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Colonic obstruction	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	6.5% 3/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.9% 2/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haematochezia	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ileal ulcer	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ileus	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	4.3% 2/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Oesophagitis	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Rectal perforation	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.9% 2/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Anal inflammation	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Subileus	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haemorrhagic ascites	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal ulcer	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	4.3% 2/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Fatigue	4.3% 2/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Performance status decreased	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Escherichia sepsis	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Sepsis	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Anal abscess	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lung infection	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	8.7% 4/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypovolaemia	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral haemorrhage	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Axitinib + FOLFIRI n=46 participants at risk Axitinib (AG-013736) tablet starting dose 5 milligram (mg) orally twice daily (BID) along with combination chemotherapy of irinotecan, 5- flurouracil (5-FU) and leucovorin (LV) (FOLFIRI) regimen consisting of irinotecan 180 mg per square meter (mg/m\^2) 90 minutes intravenous (IV) infusion, concurrently with LV 400 mg/m\^2 (or levo-leucovarin \[l-LV\] 200 mg /m\^2) 2 hours (hrs) IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFIRI n=51 participants at risk Bevacizumab 5mg/kilogram (kg) 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFIRI regimen consisting of irinotecan 180 mg/m\^2 90 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Axitinib + FOLFOX n=36 participants at risk Axitinib (AG-013736) tablet starting dose 5 mg BID along with combination chemotherapy of oxaliplatin, LV and 5-FU (FOLFOX) regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.	Bevacizumab + FOLFOX n=35 participants at risk Bevacizumab 5mg/kg 30-90 minutes IV infusion (based on tolerance) every 2 weeks along with FOLFOX regimen consisting of oxaliplatin 85 mg/m\^2 120 minutes IV infusion, concurrently with LV 400 mg/m\^2 (or l-LV 200 mg /m\^2) 2 hrs IV infusion followed immediately by 5-FU 400 mg/m\^2 IV bolus injection and a subsequent 5-FU 2400 mg/m\^2 46-48 hrs IV infusion on Day 1 of each 2 week cycle.
Investigations White blood cell count increased	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	52.2% 24/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	31.4% 16/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	36.1% 13/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	20.0% 7/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	15.2% 7/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	43.5% 20/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	52.9% 27/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	55.6% 20/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	28.6% 10/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	6.5% 3/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	7.8% 4/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	22.2% 8/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.3% 5/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure congestive	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count decreased	4.3% 2/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	13.0% 6/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	21.6% 11/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.1% 4/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.3% 5/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Coagulopathy	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukopenia	13.0% 6/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	11.8% 6/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	13.9% 5/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Left ventricular dysfunction	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachycardia	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear discomfort	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear disorder	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear pain	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders External ear inflammation	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Hyperacusis	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Otosalpingitis	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Tinnitus	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hyperthyroidism	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Endocrine disorders Hypothyroidism	15.2% 7/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	25.0% 9/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Age-related macular degeneration	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Asthenopia	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Cataract	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Conjunctival oedema	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Conjunctivitis	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Dry eye	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye discharge	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye haemorrhage	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye irritation	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.0% 1/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye pain	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.7% 2/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye pruritus	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Lacrimation increased	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.8% 1/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Mydriasis	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	2.2% 1/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Visual impairment	0.00% 0/46 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/51 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/36 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/35 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.