Combination Chemotherapy and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer - Full Text View

Sponsored by:	Federation Francophone de Cancerologie Digestive
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00628810

Purpose

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	Drug: bevacizumab Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Irinotecan Irinotecan hydrochloride Bevacizumab Fluorouracil Calcium gluconate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Chemotherapy With FOLFIRI Plus Bevacizumab (AvastinR) in Patients With Metastatic Colorectal Cancer Bearing Genotype UGT1A11/UGT1A11 or UGT1A11/UGT1A11/UGT1A1*28: Prospective, Phase II, Multicenter Study

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Objective response at 6 months by RECIST [ Designated as safety issue: No ]
Tolerability by NCI CTC v. 2.0 criteria [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Progression-free and overall survival [ Designated as safety issue: No ]
Time to treatment failure [ Designated as safety issue: No ]
Quality of life using the EuroQOL EQ5D questionnaire [ Designated as safety issue: No ]

Estimated Enrollment:	108
Study Start Date:	January 2007

Detailed Description:

OBJECTIVES:

Primary

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.

Secondary

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.

Eligibility

Ages Eligible for Study:	18 Years to 74 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00628810

Locations

France
C.H.G. Beauvais	Recruiting
Beauvais, France, 60021
Contact: Suzanne Nguyen, MD 33-34-411-2309 s.nguyen@ch-beauvais.fr
Centre Hospitalier d'Abbeville	Recruiting
Abbeville, France, 80101
Contact: Mathieu Pauwels 33-3-2225-5325
Centre Hospitalier de Chalons-en-Champagne	Recruiting
Chalons-en-Champagne, France, 51000
Contact: Naceur Abdelli, MD 33-3-2669-6051
Centre Hospitalier Departemental	Recruiting
La Roche Sur Yon, France, F-85025
Contact: Roger Faroux 33-2-5144-6168
Centre Hospitalier General Lucien Hussel	Recruiting
Vienne, France, 38200
Contact: Beatrice Eymard-Rey, MD 33-4-7431-3376 b.eymard-rey@ch-vienne.fr
Centre Hospitalier General	Recruiting
Brive, France, 19101
Contact: Laure Vayre 33-55-926-000
Centre Hospitalier Pierre Oudot	Recruiting
Bourgoin-Jallieu, France, 38300
Contact: Noel Stremsdoerfer, MD 33-4-7427-3011
Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Recruiting
Besancon, France, 25030
Contact: Anne-Claire Dupont-Gossart 33-81-668-240
Centre Hospitalier Universitaire d'Amiens	Recruiting
Amiens, France, 80054
Contact: Jean-Paul Joly 33-3-2266-8214
Centre Hospitalier Universitaire de Bicetre	Recruiting
Le Kremlin Bicetre, France, 94275
Contact: Anne Thirot-Bidault 33-1-4521-2121
Centre Regional Francois Baclesse	Recruiting
Caen, France, 14076
Contact: Karine Bouhier 33-2-3145-5000
CHR D'Orleans - Hopital de la Source	Recruiting
Orleans, France, 45100
Contact: Jean-Paul Lagasse 33-02-3651-4704
CHRU de Tours - Hopital Trousseau	Recruiting
Tours, France, 37044
Contact: Thierry Lecomte, MD 33-2-4747-5900 lecomt.t@med.univ-tours.fr
CHU - Robert Debre	Recruiting
Reims, France, 51092
Contact: Olivier Bouche, MD, PhD 33-3-2678-7169 obouche@chu-reims.fr
CHU de Caen	Recruiting
Caen, France, 14033
Contact: Karine Bouhier 33-231-063-106
CHU de la Timone	Recruiting
Marseille, France, 13385
Contact: Jean-Francois Seitz, MD 33-4-9138-6023
Polyclinique Bordeaux Nord Aquitaine	Recruiting
Bordeaux, France, 33300
Contact: Cedric Lecaille 33-556-437-354
Clinique Armoricaine De Radiologie	Recruiting
Saint Brieuc, France, F-22015
Contact: Pierre-Luc Etienne, MD 33-2-9675-22
Clinique du Tonkin	Recruiting
Villeurbanne, France, 69100
Contact: Estelle Louet 33-4-7282-6722
Clinique Mathilde	Recruiting
Rouen, France, 76100
Contact: Nicolas Albin, MD 33-2-3281-1010
Clinique Saint Vincent	Recruiting
Epernay, France, 51200
Contact: Patrick Geoffroy 33-3-2659-6135
Federation Francophone de Cancerologie Digestive	Recruiting
Dijon, France, 21079
Contact: Martina Schneider 33-3-8039-3483
Hopital Ambroise Pare	Recruiting
Boulogne-Billancourt, France, F-92104
Contact: Emmanuel Mitry, MD, PhD 33-1-4909-5874
Hopital Andre Mignot	Recruiting
Le Chesnay, France, 78157
Contact: Christine Abraham, MD 33-1-3963-8909
Hopital Bichat - Claude Bernard	Recruiting
Paris, France, 75018
Contact: Thomas Aparicio 33-1-4025-7200 thomas.aparicio@bch.ap-hop-paris.fr
Hopital Charles Nicolle	Recruiting
Rouen, France, 76031
Contact: Pierre Michel 33-2-3288-8260
Hopital de l'Archet CHU de Nice	Recruiting
Nice, France, F-06202
Contact: Francois X. Caroli-Bosc 33-4-9203-6021
Hopital Du Bocage	Recruiting
Dijon, France, 21034
Contact: Laurent Bedenne, MD 33-3-8029-3750 lbedenne@u-bourgogne.fr
Hopital Duffaut	Recruiting
Avignon, France, 84902
Contact: Ahmed Azzedine 33-4-3275-3121
Hopital Europeen Georges Pompidou	Recruiting
Paris, France, 75015
Contact: Bruno Landi, MD 33-1-5609-3555 bruno.landi@egp.aphp.fr
Hopitaux Civils de Colmar	Recruiting
Colmar, France, 68024
Contact: Gilles Breysacher, MD 33-3-8912-6097 gilles.breysacher@ch-colmar.rss
CHU Nord	Recruiting
Marseille, France, 13915
Contact: Mohamed Gasmi, MD 33-4-9196-8737

Sponsors and Collaborators

Federation Francophone de Cancerologie Digestive

Investigators

Study Chair:

Martina Schneider

Federation Francophone de Cancerologie Digestive

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000564065, FFCD-0504, EUDRACT-2006-003157-25, EU-20755
Study First Received:	March 4, 2008
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00628810
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the colon
adenocarcinoma of the rectum
stage IV colon cancer

stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Study placed in the following topic categories:

Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Irinotecan
Colonic Diseases
Leucovorin
Bevacizumab
Intestinal Diseases
Rectal Diseases
Camptothecin

Recurrence
Intestinal Neoplasms
Rectal neoplasm
Calcium, Dietary
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Angiogenesis Inhibitors

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Vitamins
Growth Inhibitors
Angiogenesis Modulating Agents
Micronutrients
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009