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

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
bevacizumab
fluorouracil
irinotecan hydrochloride
leucovorin calcium
polymorphism analysis
Sponsored by
Institut Bergonié
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, recurrent rectal cancer

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the colon or rectum

    • No other histological types

  • Metastatic, unresectable disease

    • No bone metastases only
  • Unidimensionally measurable metastatic disease
  • No CNS metastases

PATIENT CHARACTERISTICS:

  • WHO performance status (PS) 0-2 OR Karnofsky PS 70-100%
  • Life expectancy ≥ 12 weeks
  • ANC > 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 10 g/dL
  • Bilirubin ≤ 1.25 times normal (1.5 times normal in presence of hepatic metastases)
  • AST and ALT < 3 times normal (5 times normal in presence of hepatic metastases)
  • Creatinine < 1.25 times normal
  • No proteinuria
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other cancer in the past 5 years except for carcinoma in situ of the uterine cervix or basal cell skin cancer
  • No hypersensitivity to fluorouracil
  • No hypersensitivity to leucovorin calcium, bevacizumab, or their excipients
  • No hypersensitivity to Chinese hamster ovarian cell products or other recombinant humanized or nonhumanized monoclonal antibodies
  • No allergy to irinotecan hydrochloride
  • No prior reaction to attenuated vaccines (fever, jaundice)
  • No poor nutritional status
  • No Biermer anemia or other anemia due to vitamin B12 deficiency
  • No uncontrolled symptomatic occlusion or subocclusion
  • No medullary hypoplasia or severe insufficiency
  • No prior chronic intestinal disease
  • No Gilbert's syndrome
  • No intra-abdominal inflammatory reaction (e.g., gastroduodenal ulcer, diverticulitis, or colitis)
  • No chronic intestinal inflammatory disease

  • No thromboembolic arterial condition in the past 6 months, including any of the following:

    • Cardiovascular accident
    • Transient ischemic attack
    • Myocardial infarction
  • No infection or serious noncancerous disease

  • No condition that is unstable or would increase risk to the patient, including any of the following:

    • Unstable angina
    • Poorly controlled hypertension
    • Severe cardiac insufficiency
    • Serious arrhythmia
    • Bleeding diathesis
    • Pulmonary disease at risk of decompensation
  • No familial, geographical, social, or psychological condition that would preclude study participation
  • No prisoners or patients without guardians

PRIOR CONCURRENT THERAPY:

  • At least 8 weeks since prior surgery
  • At least 6 months since prior adjuvant chemotherapy
  • At least 1 month since prior palliative chemotherapy
  • No prior abdominal or pelvic radiotherapy
  • At least 30 days since prior participation in another investigational study
  • No prior bevacizumab
  • No extensive intestinal resection (e.g., partial colectomy or extensive thin resection)
  • No concurrent warfarin, Hypericum perforatum (St. John's wort), or prophylactic phenytoin

Sites / Locations

  • Institut Bergonie

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Folfiri and Bevacizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

Percentage of Participants in Objective Response (Partial or Complete Responses)
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.

Secondary Outcome Measures

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.

Full Information

First Posted
April 25, 2007
Last Updated
October 28, 2022
Sponsor
Institut Bergonié
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1. Study Identification

Unique Protocol Identification Number
NCT00467142
Brief Title
Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery
Acronym
OMEGA
Official Title
Phase II Study Evaluating the Efficacy and Tolerance to Chemotherapy With 5-fluorouracil, Folinic Acid, Irinotecan and Bevacizumab as First-line Treatment in Patients With Metastatic Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
January 23, 2007 (Actual)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Bergonié

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works as first-line therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
Detailed Description
OBJECTIVES: Primary Determine the efficacy of bevacizumab, irinotecan hydrochloride, leucovorin calcium, and fluorouracil, in terms of partial or complete response, in patients with unresectable metastatic colorectal cancer. Secondary Determine the duration of response in patients treated with this regimen. Determine the overall survival and progression-free survival of patients treated with this regimen. Determine the tolerability of this regimen in these patients. Assess the pharmacogenetics and change in genetic polymorphisms susceptible to modification by this regimen. OUTLINE: This is a nonrandomized, multicenter study. Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and bevacizumab IV on day 1. Patients also receive fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Blood and tissue samples are collected periodically for pharmacogenetic and genetic polymorphism analysis. PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, recurrent rectal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Folfiri and Bevacizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Type
Genetic
Intervention Name(s)
polymorphism analysis
Primary Outcome Measure Information:
Title
Percentage of Participants in Objective Response (Partial or Complete Responses)
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Median Duration of Response
Description
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.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum No other histological types Metastatic, unresectable disease No bone metastases only Unidimensionally measurable metastatic disease No CNS metastases PATIENT CHARACTERISTICS: WHO performance status (PS) 0-2 OR Karnofsky PS 70-100% Life expectancy ≥ 12 weeks ANC > 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 10 g/dL Bilirubin ≤ 1.25 times normal (1.5 times normal in presence of hepatic metastases) AST and ALT < 3 times normal (5 times normal in presence of hepatic metastases) Creatinine < 1.25 times normal No proteinuria Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other cancer in the past 5 years except for carcinoma in situ of the uterine cervix or basal cell skin cancer No hypersensitivity to fluorouracil No hypersensitivity to leucovorin calcium, bevacizumab, or their excipients No hypersensitivity to Chinese hamster ovarian cell products or other recombinant humanized or nonhumanized monoclonal antibodies No allergy to irinotecan hydrochloride No prior reaction to attenuated vaccines (fever, jaundice) No poor nutritional status No Biermer anemia or other anemia due to vitamin B12 deficiency No uncontrolled symptomatic occlusion or subocclusion No medullary hypoplasia or severe insufficiency No prior chronic intestinal disease No Gilbert's syndrome No intra-abdominal inflammatory reaction (e.g., gastroduodenal ulcer, diverticulitis, or colitis) No chronic intestinal inflammatory disease No thromboembolic arterial condition in the past 6 months, including any of the following: Cardiovascular accident Transient ischemic attack Myocardial infarction No infection or serious noncancerous disease No condition that is unstable or would increase risk to the patient, including any of the following: Unstable angina Poorly controlled hypertension Severe cardiac insufficiency Serious arrhythmia Bleeding diathesis Pulmonary disease at risk of decompensation No familial, geographical, social, or psychological condition that would preclude study participation No prisoners or patients without guardians PRIOR CONCURRENT THERAPY: At least 8 weeks since prior surgery At least 6 months since prior adjuvant chemotherapy At least 1 month since prior palliative chemotherapy No prior abdominal or pelvic radiotherapy At least 30 days since prior participation in another investigational study No prior bevacizumab No extensive intestinal resection (e.g., partial colectomy or extensive thin resection) No concurrent warfarin, Hypericum perforatum (St. John's wort), or prophylactic phenytoin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yves Becouarn, MD
Organizational Affiliation
Institut Bergonié
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
24758527
Citation
Becouarn Y, Cany L, Pulido M, Beyssac R, Texereau P, Le Morvan V, Bechade D, Brunet R, Aitouferoukh S, Lalet C, Mathoulin-Pelissier S, Fonck M, Robert J. FOLFIRI(R) and bevacizumab in first-line treatment for colorectal cancer patients: safety, efficacy and genetic polymorphisms. BMC Res Notes. 2014 Apr 23;7:260. doi: 10.1186/1756-0500-7-260.
Results Reference
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Bevacizumab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

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