Trial Outcomes & Findings for Study of Enzastaurin With 5-Fluorouracil/Leucovorin (5-FU/LV) Plus Bevacizumab as Maintenance Regimen Following First Line Therapy for Metastatic Colon Cancer (NCT NCT00612586)
NCT ID: NCT00612586
Last Updated: 2020-07-21
Results Overview
PFS was defined as the time from randomization to the first observation of disease progression or death due to any cause. Progressive disease was determined using a modified version of Response Evaluation Criteria in Solid Tumor (RECIST) Assessment and was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to disease progression was censored at the date of death if death was due to other cause.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
117 participants
Primary outcome timeframe
Randomization to measured progressive disease or death up to 17.2 months
Results posted on
2020-07-21
Participant Flow
Participant milestones
| Measure |
Enzastaurin + 5-FU/LV + Bev
Enzastaurin: Loading dose of 1125 milligrams (mg) orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
Leucovorin (LV): 400 mg per meter squared (mg/m\^2) intravenously (IV) on Day 1 of each 14-day cycle, followed by 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bevacizumab (Bev): 5 milligrams/kilogram (mg/kg) IV.
First-line therapy for metastatic colorectal cancer (CRC) received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5-FU/LV + Bev
Placebo: Orally 3 times during Day 1 of Cycle 1 (14-day cycle); orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) FOLFOX or FOLFIRI, plus Bev.
|
|---|---|---|
|
Overall Study
STARTED
|
58
|
59
|
|
Overall Study
Received at Least 1 Dose
|
57
|
58
|
|
Overall Study
COMPLETED
|
15
|
18
|
|
Overall Study
NOT COMPLETED
|
43
|
41
|
Reasons for withdrawal
| Measure |
Enzastaurin + 5-FU/LV + Bev
Enzastaurin: Loading dose of 1125 milligrams (mg) orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
Leucovorin (LV): 400 mg per meter squared (mg/m\^2) intravenously (IV) on Day 1 of each 14-day cycle, followed by 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bevacizumab (Bev): 5 milligrams/kilogram (mg/kg) IV.
First-line therapy for metastatic colorectal cancer (CRC) received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5-FU/LV + Bev
Placebo: Orally 3 times during Day 1 of Cycle 1 (14-day cycle); orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) FOLFOX or FOLFIRI, plus Bev.
|
|---|---|---|
|
Overall Study
Adverse Event
|
6
|
2
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Entry Criteria Not Met
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
7
|
9
|
|
Overall Study
Physician Decision
|
1
|
2
|
|
Overall Study
Sponsor Decision
|
1
|
1
|
|
Overall Study
Progressive Disease
|
26
|
24
|
|
Overall Study
Randomized and Not Treated
|
1
|
1
|
Baseline Characteristics
Study of Enzastaurin With 5-Fluorouracil/Leucovorin (5-FU/LV) Plus Bevacizumab as Maintenance Regimen Following First Line Therapy for Metastatic Colon Cancer
Baseline characteristics by cohort
| Measure |
Enzastaurin + 5-FU/LV + Bev
n=58 Participants
Enzastaurin: Loading dose of 1125 mg orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for metastatic CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5-FU/LV + Bev
n=59 Participants
Placebo: administered orally 3 times during Day 1 of Cycle 1 (14 day cycle); placebo administered orally twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
Leucovorin (LV): 400 mg/m\^2 administered by IV on Day 1 of each 14 day cycle, followed by 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bevacizumab (Bev): 5 milligrams/kilogram (mg/kg) IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Total
n=117 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.55 years
STANDARD_DEVIATION 10.90 • n=5 Participants
|
62.49 years
STANDARD_DEVIATION 9.48 • n=7 Participants
|
62.52 years
STANDARD_DEVIATION 10.16 • n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
55 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
12 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
13 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
22 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
42 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
87 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
16 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
2
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Mucinous, Not Otherwise Specified
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Adenocarcinoma, Colon
|
55 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Initial Pathological Diagnosis
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
I
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
IIa
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
IIb
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
IIIa
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
IIIb
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
IIIc
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
IV
|
47 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
|
Stage of Disease at Study Entry
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization to measured progressive disease or death up to 17.2 monthsPopulation: Intent-to-Treat (ITT) Population: All randomized participants.
PFS was defined as the time from randomization to the first observation of disease progression or death due to any cause. Progressive disease was determined using a modified version of Response Evaluation Criteria in Solid Tumor (RECIST) Assessment and was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to disease progression was censored at the date of death if death was due to other cause.
Outcome measures
| Measure |
Enzastaurin + 5-FU/LV + Bev
n=58 Participants
Enzastaurin: Loading dose of 1125 mg orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for metastatic CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5FU/LV + Bev
n=59 Participants
Placebo: Orally 3 times during Day 1 of Cycle 1 (14-day cycle); orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) FOLFOX or FOLFIRI, plus Bev.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
5.8 months
Interval 4.4 to 7.8
|
8.1 months
Interval 6.8 to 12.1
|
SECONDARY outcome
Timeframe: Randomization up to 22.8 monthsPopulation: ITT Population: All randomized participants; Number of participants censored was 54 in Placebo + 5-FU/LV + Bev treatment group.
OS was the duration from enrollment to death due to any cause. For participants who are alive, OS is censored at the last contact.
Outcome measures
| Measure |
Enzastaurin + 5-FU/LV + Bev
n=58 Participants
Enzastaurin: Loading dose of 1125 mg orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for metastatic CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5FU/LV + Bev
n=59 Participants
Placebo: Orally 3 times during Day 1 of Cycle 1 (14-day cycle); orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) FOLFOX or FOLFIRI, plus Bev.
|
|---|---|---|
|
Overall Survival (OS)
|
NA months
Interval 13.1 to
The median and upper limit of the 95% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
NA months
Interval 15.3 to
The median and upper limit of the 95% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Randomization up to 17.2 monthsPopulation: Safety Population: All randomized participants who received at least 1 dose of study drug.
A summary of serious and all other non-serious AEs is located in the Reported Adverse Event module.
Outcome measures
| Measure |
Enzastaurin + 5-FU/LV + Bev
n=57 Participants
Enzastaurin: Loading dose of 1125 mg orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for metastatic CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5FU/LV + Bev
n=58 Participants
Placebo: Orally 3 times during Day 1 of Cycle 1 (14-day cycle); orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) FOLFOX or FOLFIRI, plus Bev.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Serious AEs
|
15 Participants
|
11 Participants
|
|
Number of Participants With Adverse Events (AEs)
Other Non-Serious AEs
|
53 Participants
|
52 Participants
|
SECONDARY outcome
Timeframe: Start of first line therapy (approximately 3 months prior to randomization) to date of death from any cause up to 27 months post randomizationPopulation: ITT Population: All randomized participants; Number of participants censored were 45 in Enzastaurin + 5-FU/LV + Bev treatment group and 54 in Placebo + 5-FU/LV + Bev treatment group.
OS was the duration from first line therapy to death due to any cause. For participants who are alive, OS is censored at the last contact.
Outcome measures
| Measure |
Enzastaurin + 5-FU/LV + Bev
n=58 Participants
Enzastaurin: Loading dose of 1125 mg orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for metastatic CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5FU/LV + Bev
n=59 Participants
Placebo: Orally 3 times during Day 1 of Cycle 1 (14-day cycle); orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) FOLFOX or FOLFIRI, plus Bev.
|
|---|---|---|
|
Overall Survival (OS) From Start of First Line Therapy
|
20.0 months
Interval 15.6 to
The median and upper limit of the 95% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
NA months
Interval 19.0 to
The median and upper limit of the 95% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.
|
SECONDARY outcome
Timeframe: Start of first line therapy to measured progressive disease or death up to 24 monthsPopulation: ITT Population: All randomized participants.
PFS was defined as the time from first line therapy to the first observation of disease progression or death due to any cause. Progressive disease was determined using a modified version of RECIST Assessment and was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to disease progression was censored at the date of death if death was due to other cause.
Outcome measures
| Measure |
Enzastaurin + 5-FU/LV + Bev
n=58 Participants
Enzastaurin: Loading dose of 1125 mg orally, 3 times during Day 1 of Cycle 1 (14-day cycle); 500 mg orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for metastatic CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-FU, and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5FU/LV + Bev
n=59 Participants
Placebo: Orally 3 times during Day 1 of Cycle 1 (14-day cycle); orally, twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
LV: 400 mg/m\^2 IV on Day 1 of each 14-day cycle, followed by 5-FU 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bev: 5 mg/kg IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) FOLFOX or FOLFIRI, plus Bev.
|
|---|---|---|
|
PFS From Start of First Line Therapy
|
8.9 months
Interval 7.5 to 11.0
|
11.3 months
Interval 10.3 to 15.6
|
Adverse Events
Enzastaurin + 5-FU/LV Plus Bevacizumab
Serious events: 15 serious events
Other events: 53 other events
Deaths: 0 deaths
Placebo + 5FU/LV + Bevacizumab
Serious events: 11 serious events
Other events: 52 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Enzastaurin + 5-FU/LV Plus Bevacizumab
n=57 participants at risk
Enzastaurin: loading dose of 1125 mg administered orally 3 times during Day 1 of Cycle 1 (14 day cycle); 500 mg administered orally twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
Leucovorin (LV): 400 mg per meter squared (mg/m\^2) administered by IV on Day 1 of each 14 day cycle, followed by 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bevacizumab (Bev): 5 milligrams/kilogram (mg/kg) IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5FU/LV + Bevacizumab
n=58 participants at risk
Placebo: administered orally 3 times during Day 1 of Cycle 1 (14 day cycle); placebo administered orally twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
Leucovorin (LV): 400 mg/m\^2 administered by IV on Day 1 of each 14 day cycle, followed by 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bevacizumab (Bev): 5 milligrams/kilogram (mg/kg) IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Cardiac disorders
Arrhythmia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal hernia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Gastrointestinal disorders
Colonic obstruction
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Gastrointestinal disorders
Diarrhoea
|
5.3%
3/57 • Number of events 3
|
0.00%
0/58
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Gastrointestinal disorders
Stomatitis
|
3.5%
2/57 • Number of events 2
|
0.00%
0/58
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
General disorders
Mucosal inflammation
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
General disorders
Pyrexia
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Infections and infestations
Catheter related infection
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Infections and infestations
Device related infection
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Injury, poisoning and procedural complications
Stent malapposition
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Nervous system disorders
Intracranial venous sinus thrombosis
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Nervous system disorders
Syncope
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.8%
1/57 • Number of events 1
|
0.00%
0/58
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
7.0%
4/57 • Number of events 4
|
0.00%
0/58
|
|
Vascular disorders
Hypertensive emergency
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.00%
0/57
|
1.7%
1/58 • Number of events 1
|
Other adverse events
| Measure |
Enzastaurin + 5-FU/LV Plus Bevacizumab
n=57 participants at risk
Enzastaurin: loading dose of 1125 mg administered orally 3 times during Day 1 of Cycle 1 (14 day cycle); 500 mg administered orally twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
Leucovorin (LV): 400 mg per meter squared (mg/m\^2) administered by IV on Day 1 of each 14 day cycle, followed by 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bevacizumab (Bev): 5 milligrams/kilogram (mg/kg) IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
Placebo + 5FU/LV + Bevacizumab
n=58 participants at risk
Placebo: administered orally 3 times during Day 1 of Cycle 1 (14 day cycle); placebo administered orally twice daily on Day 2 to Day 14 of Cycle 1 and all subsequent cycles.
Leucovorin (LV): 400 mg/m\^2 administered by IV on Day 1 of each 14 day cycle, followed by 5-fluorouracil (5-FU) 400 mg/m\^2 IV bolus then 2400 mg/m\^2 IV over 46 hours, plus Bevacizumab (Bev): 5 milligrams/kilogram (mg/kg) IV.
First-line therapy for CRC received prior to entering the study: six 14-day cycles (12 weeks) folinic acid, 5-fluorouracil (5-FU), and oxaliplatin (FOLFOX) or folinic acid, 5-FU, and irinotecan (FOLFIRI), plus Bev.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.5%
6/57 • Number of events 7
|
8.6%
5/58 • Number of events 6
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.3%
3/57 • Number of events 4
|
1.7%
1/58 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
17.5%
10/57 • Number of events 14
|
12.1%
7/58 • Number of events 10
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.5%
10/57 • Number of events 11
|
13.8%
8/58 • Number of events 12
|
|
Eye disorders
Eye irritation
|
3.5%
2/57 • Number of events 2
|
5.2%
3/58 • Number of events 3
|
|
Eye disorders
Lacrimation increased
|
5.3%
3/57 • Number of events 3
|
5.2%
3/58 • Number of events 3
|
|
Eye disorders
Vision blurred
|
5.3%
3/57 • Number of events 3
|
5.2%
3/58 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal distension
|
5.3%
3/57 • Number of events 5
|
0.00%
0/58
|
|
Gastrointestinal disorders
Abdominal pain
|
17.5%
10/57 • Number of events 11
|
8.6%
5/58 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.3%
3/57 • Number of events 4
|
8.6%
5/58 • Number of events 6
|
|
Gastrointestinal disorders
Constipation
|
22.8%
13/57 • Number of events 15
|
8.6%
5/58 • Number of events 5
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
19/57 • Number of events 25
|
37.9%
22/58 • Number of events 33
|
|
Gastrointestinal disorders
Dysphagia
|
5.3%
3/57 • Number of events 3
|
0.00%
0/58
|
|
Gastrointestinal disorders
Faeces discoloured
|
8.8%
5/57 • Number of events 5
|
1.7%
1/58 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
10.5%
6/57 • Number of events 6
|
5.2%
3/58 • Number of events 3
|
|
Gastrointestinal disorders
Gingival bleeding
|
7.0%
4/57 • Number of events 4
|
0.00%
0/58
|
|
Gastrointestinal disorders
Nausea
|
26.3%
15/57 • Number of events 18
|
25.9%
15/58 • Number of events 27
|
|
Gastrointestinal disorders
Oral pain
|
8.8%
5/57 • Number of events 6
|
1.7%
1/58 • Number of events 1
|
|
Gastrointestinal disorders
Stomatitis
|
8.8%
5/57 • Number of events 5
|
6.9%
4/58 • Number of events 4
|
|
Gastrointestinal disorders
Vomiting
|
12.3%
7/57 • Number of events 7
|
17.2%
10/58 • Number of events 15
|
|
General disorders
Asthenia
|
5.3%
3/57 • Number of events 3
|
0.00%
0/58
|
|
General disorders
Chills
|
5.3%
3/57 • Number of events 3
|
1.7%
1/58 • Number of events 1
|
|
General disorders
Fatigue
|
42.1%
24/57 • Number of events 29
|
39.7%
23/58 • Number of events 29
|
|
General disorders
Mucosal inflammation
|
15.8%
9/57 • Number of events 12
|
15.5%
9/58 • Number of events 12
|
|
General disorders
Pain
|
5.3%
3/57 • Number of events 3
|
0.00%
0/58
|
|
General disorders
Pyrexia
|
10.5%
6/57 • Number of events 7
|
12.1%
7/58 • Number of events 8
|
|
Infections and infestations
Nasopharyngitis
|
5.3%
3/57 • Number of events 3
|
3.4%
2/58 • Number of events 3
|
|
Infections and infestations
Sinusitis
|
5.3%
3/57 • Number of events 3
|
1.7%
1/58 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
8.8%
5/57 • Number of events 5
|
5.2%
3/58 • Number of events 3
|
|
Investigations
Alanine aminotransferase increased
|
8.8%
5/57 • Number of events 5
|
10.3%
6/58 • Number of events 7
|
|
Investigations
Aspartate aminotransferase increased
|
7.0%
4/57 • Number of events 4
|
8.6%
5/58 • Number of events 5
|
|
Investigations
Blood creatinine increased
|
3.5%
2/57 • Number of events 2
|
5.2%
3/58 • Number of events 3
|
|
Investigations
Haemoglobin decreased
|
10.5%
6/57 • Number of events 6
|
3.4%
2/58 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
5.3%
3/57 • Number of events 3
|
3.4%
2/58 • Number of events 2
|
|
Investigations
Urine colour abnormal
|
12.3%
7/57 • Number of events 7
|
0.00%
0/58
|
|
Investigations
Weight decreased
|
8.8%
5/57 • Number of events 5
|
0.00%
0/58
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.8%
9/57 • Number of events 10
|
12.1%
7/58 • Number of events 7
|
|
Metabolism and nutrition disorders
Dehydration
|
5.3%
3/57 • Number of events 3
|
3.4%
2/58 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
8.8%
5/57 • Number of events 5
|
5.2%
3/58 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.3%
3/57 • Number of events 3
|
1.7%
1/58 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.3%
3/57 • Number of events 3
|
0.00%
0/58
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
1.8%
1/57 • Number of events 1
|
6.9%
4/58 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.3%
7/57 • Number of events 7
|
8.6%
5/58 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.3%
3/57 • Number of events 3
|
10.3%
6/58 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.3%
3/57 • Number of events 4
|
5.2%
3/58 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
8.8%
5/57 • Number of events 5
|
5.2%
3/58 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
10.5%
6/57 • Number of events 6
|
10.3%
6/58 • Number of events 11
|
|
Nervous system disorders
Dysgeusia
|
3.5%
2/57 • Number of events 2
|
5.2%
3/58 • Number of events 3
|
|
Nervous system disorders
Headache
|
17.5%
10/57 • Number of events 17
|
13.8%
8/58 • Number of events 12
|
|
Nervous system disorders
Neuropathy peripheral
|
7.0%
4/57 • Number of events 5
|
1.7%
1/58 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
7.0%
4/57 • Number of events 5
|
3.4%
2/58 • Number of events 4
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
10.5%
6/57 • Number of events 7
|
13.8%
8/58 • Number of events 8
|
|
Nervous system disorders
Polyneuropathy
|
5.3%
3/57 • Number of events 3
|
6.9%
4/58 • Number of events 4
|
|
Nervous system disorders
Somnolence
|
7.0%
4/57 • Number of events 5
|
1.7%
1/58 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
5.3%
3/57 • Number of events 3
|
1.7%
1/58 • Number of events 1
|
|
Psychiatric disorders
Depression
|
5.3%
3/57 • Number of events 3
|
1.7%
1/58 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
5.3%
3/57 • Number of events 3
|
5.2%
3/58 • Number of events 3
|
|
Renal and urinary disorders
Chromaturia
|
7.0%
4/57 • Number of events 4
|
0.00%
0/58
|
|
Renal and urinary disorders
Proteinuria
|
10.5%
6/57 • Number of events 6
|
6.9%
4/58 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.8%
13/57 • Number of events 17
|
19.0%
11/58 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.5%
6/57 • Number of events 7
|
8.6%
5/58 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
28.1%
16/57 • Number of events 20
|
22.4%
13/58 • Number of events 16
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.0%
4/57 • Number of events 5
|
6.9%
4/58 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.0%
4/57 • Number of events 4
|
3.4%
2/58 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
3.5%
2/57 • Number of events 2
|
10.3%
6/58 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.8%
5/57 • Number of events 5
|
8.6%
5/58 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.5%
6/57 • Number of events 6
|
6.9%
4/58 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
3.5%
2/57 • Number of events 2
|
5.2%
3/58 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
15.8%
9/57 • Number of events 16
|
24.1%
14/58 • Number of events 18
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/57
|
6.9%
4/58 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.0%
8/57 • Number of events 9
|
8.6%
5/58 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
5.3%
3/57 • Number of events 3
|
3.4%
2/58 • Number of events 2
|
|
Vascular disorders
Hypertension
|
12.3%
7/57 • Number of events 7
|
22.4%
13/58 • Number of events 17
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60