Combination Chemotherapy and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00628810
• Other study ID #: CDR0000564065
• Secondary ID: FFCD-0504EUDRACT
• Status: Completed
• Phase: Phase 2
• Start date: January 2007
• Est. completion date: December 2008

Study information

• Verified date: November 2020
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: December 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• fluorouracil

• irinotecan hydrochloride

• leucovorin calcium

Locations

Country	Name	City	State
France	Centre Hospitalier d'Abbeville	Abbeville
France	Centre Hospitalier Universitaire d'Amiens	Amiens
France	Hopital Duffaut	Avignon
France	C.H.G. Beauvais	Beauvais
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Hopital Ambroise Pare	Boulogne-Billancourt
France	Centre Hospitalier Pierre Oudot	Bourgoin-Jallieu
France	Centre Hospitalier General	Brive
France	Centre Regional Francois Baclesse	Caen
France	CHU de Caen	Caen
France	Centre Hospitalier de Chalons-en-Champagne	Chalons-en-Champagne
France	Hopitaux Civils de Colmar	Colmar
France	Federation Francophone de Cancerologie Digestive	Dijon
France	Hopital Du Bocage	Dijon
France	Clinique Saint Vincent	Epernay
France	Centre Hospitalier Departemental	La Roche Sur Yon
France	Hopital Andre Mignot	Le Chesnay
France	Centre Hospitalier Universitaire de Bicetre	Le Kremlin Bicetre
France	CHU de la Timone	Marseille
France	CHU Nord	Marseille
France	Hopital de l'Archet CHU de Nice	Nice
France	CHR D'Orleans - Hopital de la Source	Orleans
France	Hopital Bichat - Claude Bernard	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	CHU - Robert Debre	Reims
France	Clinique Mathilde	Rouen
France	Hopital Charles Nicolle	Rouen
France	Clinique Armoricaine De Radiologie	Saint Brieuc
France	CHRU de Tours - Hopital Trousseau	Tours
France	Centre Hospitalier General Lucien Hussel	Vienne
France	Clinique du Tonkin	Villeurbanne

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

References & Publications (1)

Manfredi S, Bouché O, Rougier P, Dahan L, Loriot MA, Aparicio T, Etienne PL, Lafargue JP, Lécaille 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 Treatme — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response at 6 months by RECIST		6 months
Primary	Tolerability evaluated by NCI CTC v. 2.0 criteria		From Inclusion
Secondary	Progression-free and overall survival		From Inclusion
Secondary	Time to treatment failure		From Inclusion
Secondary	Quality of life using the EuroQOL EQ5D questionnaire		From Inclusion