Trial Outcomes & Findings for Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery (NCT NCT00467142)

Last Updated: 2022-11-01

Results Overview

Objective response defined as complete or partial responses according to RECIST v1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.).Radiologic assessment was carried out every four cycles (8 weeks) with centralized external secondary review.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

62 participants

Primary outcome timeframe

6 months

Results posted on

2022-11-01

Participant Flow

Participant milestones

Participant milestones
Measure	Folfiri and Bevacizumab * Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated. bevacizumab fluorouracil irinotecan hydrochloride leucovorin calcium polymorphism analysis
Overall Study STARTED	62
Overall Study COMPLETED	59
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Folfiri and Bevacizumab * Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated. bevacizumab fluorouracil irinotecan hydrochloride leucovorin calcium polymorphism analysis
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1
Overall Study Protocol Violation	1

Baseline Characteristics

Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Folfiri and Bevacizumab n=62 Participants * Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated. bevacizumab fluorouracil irinotecan hydrochloride leucovorin calcium polymorphism analysis
Age, Continuous	67.9 years n=5 Participants
Sex: Female, Male Female	37 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants
Region of Enrollment France	62 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Folfiri and Bevacizumab n=59 Participants * Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated. bevacizumab fluorouracil irinotecan hydrochloride leucovorin calcium polymorphism analysis
Percentage of Participants in Objective Response (Partial or Complete Responses)	47.5 percentage of participants Interval 34.3 to 60.9

SECONDARY outcome

Timeframe: 24 months

Population: 28 patients in partial response were evaluable for median duration of response.

Duration of response is defined as the delay between response (complete or partial) and disease progression according to RECIST V1.0. Therefore, this criterion can only be assessed in in subjects who have responded. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.). Progression is defined as a 20% increase in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, or appearance of one or several new lesions (RECIST V1.0) Radiologic assessment was carried out every four cycles (8 weeks) with centralized external secondary review.

Outcome measures

Outcome measures
Measure	Folfiri and Bevacizumab n=28 Participants * Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated. bevacizumab fluorouracil irinotecan hydrochloride leucovorin calcium polymorphism analysis
Median Duration of Response	9.5 months Interval 2.7 to 20.0

Adverse Events

Folfiri and Bevacizumab

Serious events: 20 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Folfiri and Bevacizumab n=62 participants at risk * Premedication = Dexchlorpheniramine, 5 mg in slow Direct IntraVeinous (DIV) on D1. * FOLFIRI (simplified LV5FU2 + irinotecan): * Irinotecan (Campto®): 180 mg/m² on D1 by IV infusion in 250 mL of 0.9% saline over 90 minutes. * LV5FU2, in its so-called "simplified" version, will be administered as follows L-folinic acid, as a 2-hour intravenous infusion, at a dose of 200 mg/m², on Day 1, in 500 mL of 5% glucose solution, concomitantly with the irinotecan infusion via a Y-tube, followed by 5 Fluorouracil (5 FU), intravenous bolus, at a dose of 400 mg/m² on D1, followed by 5 Fluorouracil (5 FU) as a 46-hour continuous infusion at a dose of 2400 mg/m² from D1 to D3, either in 1000 mL of 5% glucose solution, or in an electric syringe or pump dispenser * Bevacizumab (Avastin®): 5 mg/kg IV infusion in 100 mL of 0.9% saline over 90 minutes for the first infusion, then 60 minutes for the second infusion if tolerated, and 30 minutes for subsequent infusions if tolerated. bevacizumab fluorouracil irinotecan hydrochloride leucovorin calcium polymorphism analysis
Gastrointestinal disorders Diarrhea	4.8% 3/62 • Number of events 3 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Gastrointestinal disorders Colitis	3.2% 2/62 • Number of events 2 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
General disorders Fatigue	3.2% 2/62 • Number of events 2 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Gastrointestinal disorders Obstruction	3.2% 2/62 • Number of events 2 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Gastrointestinal disorders Gastritis	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Metabolism and nutrition disorders Anorexia	3.2% 2/62 • Number of events 2 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Infections and infestations Bronchial infection	3.2% 2/62 • Number of events 3 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Vascular disorders Phlebitis	3.2% 2/62 • Number of events 2 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Gastrointestinal disorders Anal fistula	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Infections and infestations Bladder infection	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Infections and infestations Breast infection	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Metabolism and nutrition disorders Hyponatremia	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Nervous system disorders Neuralgia	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Injury, poisoning and procedural complications RESTORATION OF COLORECTAL CONTINUITY	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Injury, poisoning and procedural complications PORTAL EMBOLISATION	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Blood and lymphatic system disorders White blood cell decreased	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
General disorders DETERIORATION OF GENERAL HEALTH STATUS	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Cardiac disorders Atrial fibrillaton	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Vascular disorders Myocardial infarction	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.
Renal and urinary disorders RENAL FAILURE	1.6% 1/62 • Number of events 1 Only serious adverse events were monitored. Adverse events (non-serious) were not assessed/monitored during the study.

Other adverse events

Adverse event data not reported

Additional Information

Pr Yves Becouran

Institut Bergonié

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place