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Combination Chemotherapy and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

This study has been completed.
Information provided by (Responsible Party):
Federation Francophone de Cancerologie Digestive Identifier:
First received: March 4, 2008
Last updated: May 27, 2016
Last verified: May 2016

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 tumor cells by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving combination chemotherapy together with bevacizumab and to see how well it works in treating patients with metastatic colorectal cancer.

Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Chemotherapy With FOLFIRI Plus Bevacizumab (AvastinR) in Patients With Metastatic Colorectal Cancer Bearing Genotype UGT1A1*1/UGT1A1*1 or UGT1A1*1/UGT1A1*1/UGT1A1*28: Prospective, Phase II, Multicenter Study

Resource links provided by NLM:

Further study details as provided by Federation Francophone de Cancerologie Digestive:

Primary Outcome Measures:
  • Objective response at 6 months by RECIST [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Tolerability evaluated by NCI CTC v. 2.0 criteria [ Time Frame: From Inclusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Progression-free and overall survival [ Time Frame: From Inclusion ] [ Designated as safety issue: No ]
  • Time to treatment failure [ Time Frame: From Inclusion ] [ Designated as safety issue: No ]
  • Quality of life using the EuroQOL EQ5D questionnaire [ Time Frame: From Inclusion ] [ Designated as safety issue: No ]

Enrollment: 86
Study Start Date: January 2007
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFIRI fort plus bevacizumab
Bevacizumab 5 mg/kg D1, irinotecan 260 mg/m2 D1, LV 400 mg/m2 D1, 5FU 400 mg/m2 IV bolus D1, and 5FU 2,400 mg/m2 46-hour infusion D1-2 every 2 weeks. Treatment was started within 2 weeks after inclusion in the study.
Biological: bevacizumab Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium

Detailed Description:



  • Evaluate the objective response (RECIST criteria) at 6 months associated with FOLFIRI and bevacizumab therapy.
  • Evaluate the tolerability (NCI CTC v. 2.0 criteria) of this treatment.


  • Evaluate progression-free survival and overall survival.
  • Determine the time to treatment failure.
  • Evaluate the quality of life (EuroQOL EQ5D questionnaire).
  • Explore the prognostic factors associated with the tolerability and efficacy of this treatment.

OUTLINE: This is a multicenter study. Patients are stratified according to genotype (UCT1A1*1/ UCT1A1*1 vs UCT1A1*1/ UCT1A1*28).

Patients receive bevacizumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 4 courses, and then every 2 months after the completion of study therapy.

After completion of study therapy, patients are followed every 2-3 months.


Ages Eligible for Study:   18 Years to 74 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Diagnosis of metastatic adenocarcinoma of the colon or rectum

    • Not curable by surgery
  • Genotype UGT1A1*1/UGT1A1*1 or UGT1A1*1/ UGT1A1*28
  • Measurable disease
  • No original tumor in place
  • No secondary cerebral metastases


Inclusion criteria:

  • WHO performance status 0-2
  • Life expectancy ≥ 3 months
  • Absolute neutrophil count ≥ 1,500/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 times normal
  • Alkaline phosphatase ≤ 2.5 times normal (5 times normal if liver involvement)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients of must use effective contraception

Exclusion criteria:

  • Progressive gastrointestinal ulcer, hemorrhagic ulcer, or perforation in the past 6 months
  • Enteropathy or chronic diarrhea
  • Proteinuria > 500 mg/24 hours
  • Active cardiac disease
  • Uncontrolled hypertension
  • Myocardial infarction in the past 12 months
  • Angina
  • NYHA grade II-IV congestive heart disease
  • Severe arrhythmia even with treatment
  • Peripheral vascular disease ≥ grade II
  • Nonhealing wound, ulcer, or severe bone fracture
  • Hemorrhagic diatheses or coagulopathy
  • Severe or uncontrolled infection
  • Severe or uncontrolled medical condition
  • Other malignant disease in the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the uterine cervix
  • Severe traumatic injury within the past 4 weeks


  • No prior chemotherapy for metastatic disease

    • One prior regimen of chemotherapy in the neoadjuvant or adjuvant setting for the original tumor allowed
  • At least 6 months since prior chemotherapy
  • No prior irinotecan hydrochloride or bevacizumab
  • No oral or parenteral anticoagulant therapy within the past 10 days

    • Warfarin allowed provided INR < 1.5
  • No major surgery or biopsy within the past 4 weeks
  • No puncture in the past 7 days
  • No planned major surgery
  • No concurrent daily or chronic aspirin (> 325 mg/day), anti-inflammatories, or steroids
  • No other concurrent anticancer therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00628810

Centre Hospitalier d'Abbeville
Abbeville, France, 80101
Centre Hospitalier Universitaire d'Amiens
Amiens, France, 80054
Hopital Duffaut
Avignon, France, 84902
C.H.G. Beauvais
Beauvais, France, 60021
Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
Besancon, France, 25030
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, France, 33300
Hopital Ambroise Pare
Boulogne-Billancourt, France, F-92104
Centre Hospitalier Pierre Oudot
Bourgoin-Jallieu, France, 38300
Centre Hospitalier General
Brive, France, 19101
CHU de Caen
Caen, France, 14033
Centre Regional Francois Baclesse
Caen, France, 14076
Centre Hospitalier de Chalons-en-Champagne
Chalons-en-Champagne, France, 51000
Hopitaux Civils de Colmar
Colmar, France, 68024
Hopital Du Bocage
Dijon, France, 21034
Federation Francophone de Cancerologie Digestive
Dijon, France, 21079
Clinique Saint Vincent
Epernay, France, 51200
Centre Hospitalier Departemental
La Roche Sur Yon, France, F-85025
Hopital Andre Mignot
Le Chesnay, France, 78157
Centre Hospitalier Universitaire de Bicetre
Le Kremlin Bicetre, France, 94275
CHU de la Timone
Marseille, France, 13385
CHU Nord
Marseille, France, 13915
Hopital de l'Archet CHU de Nice
Nice, France, F-06202
CHR D'Orleans - Hopital de la Source
Orleans, France, 45100
Hopital Europeen Georges Pompidou
Paris, France, 75015
Hopital Bichat - Claude Bernard
Paris, France, 75018
CHU - Robert Debre
Reims, France, 51092
Hopital Charles Nicolle
Rouen, France, 76031
Clinique Mathilde
Rouen, France, 76100
Clinique Armoricaine De Radiologie
Saint Brieuc, France, F-22015
CHRU de Tours - Hopital Trousseau
Tours, France, 37044
Centre Hospitalier General Lucien Hussel
Vienne, France, 38200
Clinique du Tonkin
Villeurbanne, France, 69100
Sponsors and Collaborators
Federation Francophone de Cancerologie Digestive
Study Chair: Martina Schneider Federation Francophone de Cancerologie Digestive
  More Information

Responsible Party: Federation Francophone de Cancerologie Digestive Identifier: NCT00628810     History of Changes
Other Study ID Numbers: CDR0000564065  FFCD-0504  EUDRACT-2006-003157-25  EU-20755 
Study First Received: March 4, 2008
Last Updated: May 27, 2016
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Federation Francophone de Cancerologie Digestive:
adenocarcinoma of the colon
adenocarcinoma of the rectum
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors processed this record on October 20, 2016