Combination Chemotherapy and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

Federation Francophone de Cancerologie Digestive

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: fluorouracil; Drug: irinotecan hydrochloride; Biological: bevacizumab; Drug: leucovorin calcium

Study type: Interventional

Funder types: Other

Identifiers

NCT00628810

EUDRACT-2006-003157-25

FFCD-0504

EU-20755

CDR0000564065

Details and patient eligibility

About

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.

Full 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.

Enrollment: 86 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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86 participants in 1 patient group

FOLFIRI fort plus bevacizumab

Experimental group

Description:

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.

Treatment:

Biological: bevacizumab

Drug: leucovorin calcium

Drug: fluorouracil

Drug: irinotecan hydrochloride