Bevacizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

NCT ID: NCT00797485

Last Updated: 2013-08-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 672 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31

Brief Summary

RATIONALE: 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. 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. Giving bevacizumab together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase III trial is studying how well giving induction therapy with bevacizumab together with combination chemotherapy with or without capecitabine followed by bevacizumab maintenance therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• To compare two strategies of induction bio-chemotherapy followed by the same maintenance biotherapy in terms of time to failure in patients with previously untreated metastatic colorectal cancer.

Secondary

• To compare the two arms of treatment in terms of response rate, duration of responses, progression-free survival, safety, and quality of life of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment center, performance status (0 vs 1), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2 induction therapy arms.

• Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

In both arms, patients achieving stable disease after completion of 6 months of induction therapy proceed to maintenance therapy.

• Maintenance therapy: Patients receive bevacizumab IV over 30-90 minutes every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

During or after completion of maintenance therapy, patients with tumor regrowth that is not classified as disease progression from baseline and who achieved partial or complete response during or after their induction therapy proceed to reinduction therapy.

• Reinduction therapy: Patients receive B-FOLFIRI as described previously. Quality of life is assessed at baseline, every 3 months during induction therapy, and at discontinuation of study therapy.

After completion of study therapy, patients are followed for up to 2 years.

Conditions

Colorectal Cancer

Keywords

stage IV colon cancer; stage IV rectal cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type: ACTIVE_COMPARATOR

bevacizumab

Intervention Type: BIOLOGICAL

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

leucovorin calcium

Intervention Type: DRUG

Given IV

Arm II

Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

Given IV

capecitabine

Intervention Type: DRUG

Given orally

fluorouracil

Intervention Type: DRUG

Given IV

irinotecan hydrochloride

Intervention Type: DRUG

Given IV

leucovorin calcium

Intervention Type: DRUG

Given IV

Interventions

bevacizumab

Given IV

Intervention Type: BIOLOGICAL

capecitabine

Given orally

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

irinotecan hydrochloride

Given IV

Intervention Type: DRUG

leucovorin calcium

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer

• Metastatic disease that is not amenable to surgery
• At least one measurable lesion according to RECIST criteria
• No untreated brain metastases or spinal cord compression

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy ≥ 12 weeks
• Hemoglobin ≥ 9.0 g/dL
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
• Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
• PT-INR/PTT < 1.5 times ULN
• Creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 times ULN
• Proteinuria on dipstick urinalysis < 2+ OR 24-hour urine protein ≤ 1g
• Not pregnant or nursing
• Negative pregnancy test
• Must be accessible for treatment and follow-up
• No history of inflammatory bowel disease and/or acute or subacute bowel occlusion
• No serious non-healing wound, ulcer, or bone fracture
• No evidence of bleeding diathesis or coagulopathy
• No uncontrolled hypertension
• No clinically significant cardiovascular disease including any of the following:

• Cerebrovascular accident within the past 6 months
• Myocardial infarction within the past 6 months
• Unstable angina
• New York Heart Association grade II-IV congestive heart failure
• Serious cardiac arrhythmia requiring medication
• No known allergy to Chinese hamster ovary cell proteins or any of the components of the study medications
• No other malignancy within the past 5 years except basal cell and squamous cell skin cancer or carcinoma in situ of the cervix
• No significant traumatic injury within the past 28 days
• No substance abuse or medical, psychological, or social conditions that may interfere with participation in the study or the evaluation of study results
• Able to swallow oral medications

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 6 months since prior adjuvant treatment
• No prior irinotecan and/or bevacizumab during prior adjuvant therapy
• No prior cytotoxic drugs for the metastatic disease
• More than 10 days since prior and no concurrent anticoagulants for therapeutic purposes
• No chronic, daily treatment with high-dose aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration
• No treatment with any investigational drug within the past 30 days
• No major surgical procedure or open biopsy within the past 28 days or anticipated need for a major surgical procedure during the course of the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Southern Italy Cooperative Oncology Group

OTHER

Sponsor Role: lead

Principal Investigators

Pasquale Comella, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Nazionale per lo Studio e la Cura dei Tumori

Locations

Southern Italy Cooperative Oncology Group

Naples, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

Pasquale Comella, MD

Role: primary

Other Identifiers

SICOG-0803

Identifier Type: -

Identifier Source: secondary_id

EudraCT-2008-004890-17

Identifier Type: -

Identifier Source: secondary_id

CDR0000617983

Identifier Type: -

Identifier Source: org_study_id