Clinical trial NCT00628810: Combination Chemotherapy and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the colon
adenocarcinoma of the rectum
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2008-03-05
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Objective response at 6 months by RECIST
timeFrame: 6 months
measure: Tolerability evaluated by NCI CTC v. 2.0 criteria
timeFrame: From Inclusion
Secondary outcomes:
measure: Progression-free and overall survival
timeFrame: From Inclusion
measure: Time to treatment failure
timeFrame: From Inclusion
measure: Quality of life using the EuroQOL EQ5D questionnaire
timeFrame: From Inclusion
Other outcomes:
Locations:
city: Abbeville
country: France
facility: Centre Hospitalier d'Abbeville
city: Amiens
country: France
facility: Centre Hospitalier Universitaire d'Amiens
city: Avignon
country: France
facility: Hopital Duffaut
city: Beauvais
country: France
facility: C.H.G. Beauvais
city: Besancon
country: France
facility: Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Pare
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier Pierre Oudot
city: Brive
country: France
facility: Centre Hospitalier General
city: Caen
country: France
facility: CHU de Caen
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Chalons-en-Champagne
country: France
facility: Centre Hospitalier de Chalons-en-Champagne
city: Colmar
country: France
facility: Hopitaux Civils de Colmar
city: Dijon
country: France
facility: Hopital Du Bocage
city: Dijon
country: France
facility: Federation Francophone de Cancerologie Digestive
city: Epernay
country: France
facility: Clinique Saint Vincent
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
city: Le Kremlin Bicetre
country: France
facility: Centre Hospitalier Universitaire de Bicetre
city: Marseille
country: France
facility: CHU de la Timone
city: Marseille
country: France
facility: CHU Nord
city: Nice
country: France
facility: Hopital de l'Archet CHU de Nice
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Reims
country: France
facility: CHU - Robert Debre
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Rouen
country: France
facility: Clinique Mathilde
city: Saint Brieuc
country: France
facility: Clinique Armoricaine De Radiologie
city: Tours
country: France
facility: CHRU de Tours - Hopital Trousseau
city: Vienne
country: France
facility: Centre Hospitalier General Lucien Hussel
city: Villeurbanne
country: France
facility: Clinique du Tonkin
Study officials:
affiliation: Federation Francophone de Cancerologie Digestive
name: Martina Schneider
role: STUDY_CHAIR
References:
citation: Manfredi S, Bouche O, Rougier P, Dahan L, Loriot MA, Aparicio T, Etienne PL, Lafargue JP, Lecaille C, Legoux JL, Le Malicot K, Maillard E, Lecomte T, Khemissa F, Breysacher G, Michel P, Mitry E, Bedenne L. High-Dose FOLFIRI plus Bevacizumab in the Treatment of Metastatic Colorectal Cancer Patients with Two Different UGT1A1 Genotypes: FFCD 0504 Study. Mol Cancer Ther. 2015 Dec;14(12):2782-8. doi: 10.1158/1535-7163.MCT-15-0293. Epub 2015 Oct 22.