Trial Outcomes & Findings for Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer (NCT NCT00555672)

NCT ID: NCT00555672

Last Updated: 2011-12-19

Results Overview

The incidence of DLTs assessed during the first cycle (21 days).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

Cycle 1 (Baseline to Day 21)

Results posted on

2011-12-19

Participant Flow

Participant milestones

Participant milestones
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Overall Study STARTED	24	10
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	24	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Overall Study Death	0	2
Overall Study Adverse Event	8	2
Overall Study Objective progression or relapse	11	5
Overall Study Other	3	1
Overall Study Participant refused	2	0

Baseline Characteristics

Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=24 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU n=10 Participants Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Total n=34 Participants Total of all reporting groups
Age Continuous	60.1 years STANDARD_DEVIATION 12.0 • n=5 Participants	56.4 years STANDARD_DEVIATION 10.4 • n=7 Participants	59.0 years STANDARD_DEVIATION 11.5 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	6 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (Baseline to Day 21)

Population: Safety: enrolled participants who received at least 1 dose of study drug.

The incidence of DLTs assessed during the first cycle (21 days).

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=24 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU n=10 Participants Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Number of Participants With First-cycle Dose Limiting Toxicities (DLTs)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose)

Population: Pharmacokinetic (PK): participants who received Sunitinib and had sufficient plasma concentration data for calculation of PK parameters; N=number of participants contributing to summary statistics. Cmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) calculated for at least 6 individual participants treated at maximum tolerated dose.

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=9 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Maximum Observed Plasma Concentration (Cmax) Sunitinib	16.8 nanograms per milliliter (ng/mL) Standard Deviation 8.19	—
Maximum Observed Plasma Concentration (Cmax) SU012662 (metabolite of Sunitinib)	2.24 nanograms per milliliter (ng/mL) Standard Deviation 1.29	—
Maximum Observed Plasma Concentration (Cmax) Total Drug (Sunitinib + SU012662)	19.0 nanograms per milliliter (ng/mL) Standard Deviation 9.35	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours postdose)

Population: PK; N=the number of participants contributing to the summary statistics. AUC(0-24) of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) calculated for at least 6 individual participants treated at the maximum tolerated dose (MTD; 25 mg Sunitinib).

Area under the plasma concentration versus time curve from time 0 (pre-dose) to 24 hours postdose (0-24).

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=9 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Area Under the Curve From Time 0 to 24 Hours Postdose [AUC (0-24)] Sunitinib	249 ng*h/mL Standard Deviation 127	—
Area Under the Curve From Time 0 to 24 Hours Postdose [AUC (0-24)] SU012662 (metabolite of Sunitinib)	34.0 ng*h/mL Standard Deviation 19.5	—
Area Under the Curve From Time 0 to 24 Hours Postdose [AUC (0-24)] Total Drug (Sunitinib + SU012662)	283 ng*h/mL Standard Deviation 144	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (2, 4, 6, 8, 10, and 24 hours post dose)

Population: PK; N=the number of participants contributing to the summary statistics. Tmax of Sunitinib, SU012662, and Total Drug (Sunitinib + SU012662) calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Tmax is the time to first occurrence of maximum observed plasma concentration (Cmax).

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=9 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Time to Reach Maximum Observed Plasma Concentration (Tmax) Sunitinib	4.00 hours Interval 2.0 to 24.0	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) SU012662 (metabolite of Sunitinib)	4.00 hours Interval 2.0 to 24.0	—
Time to Reach Maximum Observed Plasma Concentration (Tmax) Total Drug (Sunitinib + SU012662)	4.00 hours Interval 2.0 to 24.0	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Population: PK; N=number of participants contributing to the summary statistics. Css calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Steady state plasma concentration of 5-FU equals AUC(2-6) divided by 4, where AUC(2-6) is the area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6).

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=6 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Steady State Concentration (Css) of 5-Fluorouracil (5-FU)	593 ng/mL Standard Deviation 433	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Population: PK; N= number of participants contributing to the summary statistics. R0 calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Infusion rate of 5-FU equals total dose divided by infusion time.

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=6 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Infusion Rate (Zero Order) (R0) of 5-FU	68.2 mg/hr Standard Deviation 12.5	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Population: PK; N=the number of participants contributing to the summary statistics. CLss calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Steady state total body clearance equals infusion rate (zero order) divided by steady state plasma concentration of 5-FU (R0/Css).

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=6 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Clearance (CLss) of 5-FU	161 Liters per hour Standard Deviation 93.2	—

SECONDARY outcome

Timeframe: Day 1 of Cycle 1 (2, 4, and 6 hours post infusion)

Population: PK; N=number of participants contributing to the summary statistics. Css calculated for at least 6 individual participants treated at the MTD (25 mg Sunitinib).

Area under the plasma concentration versus time curve from time 2 to 6 hours postdose (2-6).

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=6 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Area Under the Curve From Time 2 to 6 Hours Postdose [AUC (2-6)] of 5-FU	2372 ng*h/mL Standard Deviation 1729	—

SECONDARY outcome

Timeframe: Baseline, Day 21 of every even-numbered cycle up to 15 Months

Population: Efficacy: all participants enrolled in the study who received at least 1 dose of study medication. N=number of participants with measurable disease at baseline.

Number of participants with an objective response-based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as the disappearance of all target lesions. PR defined as greater than or equal to (≥) 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=23 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU n=10 Participants Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Number of Participants With Objective Response	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline up to Month 15

Population: Efficacy; N=number of participants with objective response.

Time from the first objective documentation of tumor response (confirmed or partial response) to first documented objective tumor progression or death due to any cause, whichever occurrs first. DR calculated as (Months) equals (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 30.

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=6 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU n=3 Participants Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Duration of Response (DR)	4.17 Months Standard Deviation 2.28	4.13 Months Standard Deviation 0.73

SECONDARY outcome

Timeframe: Baseline up to Month 15

Population: Efficacy

Median time (50%) from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. PFS calculated as (Months) equals (first event date minus first dose date plus 1) divided by 30.

Outcome measures

Outcome measures
Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=24 Participants Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU n=10 Participants Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Progression-Free Survival (PFS)	5.2 Months Interval 3.8 to 7.6	6.2 Months Interval 3.3 to 6.9

Adverse Events

Sunitinib (25 mg) in Combination With Cisplatin and 5-FU

Serious events: 7 serious events

Other events: 24 other events

Deaths: 0 deaths

Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU

Serious events: 5 serious events

Other events: 10 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

Measure	Sunitinib (25 mg) in Combination With Cisplatin and 5-FU n=24 participants at risk Sunitinib: 25 milligram (mg) oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) intravenous on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.	Sunitinib (37.5 mg) in Combination With Cisplatin and 5-FU n=10 participants at risk Sunitinib: 37.5 mg oral capsule daily for 2 weeks (Day 1 to 14) followed by 1 week (Day 15 to 21) off treatment. Cisplatin: 80 mg per meter squared (mg/m\^2) on Day 1 of each 21-day cycle. 5-Fluorouracil (5-FU): 4000 mg/m\^2 continuous infusion for 96 hours starting Day 1 and ending Day 5 of each 21-day cycle.
Blood and lymphatic system disorders Anaemia	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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	4.2% 1/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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% 2/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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	8.3% 2/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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% 0/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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 Myocardial ischaemia	4.2% 1/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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% 0/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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 perforation	4.2% 1/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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% 0/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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 Device occlusion	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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 Mucosal inflammation	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	30.0% 3/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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 Pyrexia	4.2% 1/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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% 0/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure acute	4.2% 1/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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% 0/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	8.3% 2/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious 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% 0/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Rash	0.00% 0/24 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 1/10 The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.