Bevacizumab and Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

Phase II Study Evaluating the Association of Bevacizumab and Chemotherapy of the Type Modified FOLFIRI 3 in Patients With Metastatic Colorectal Adenocarcinoma

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, such as irinotecan, fluorouracil, and capecitabine, 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 II trial is studying how well bevacizumab given together with combination chemotherapy works in treating patients with metastatic colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: irinotecan hydrochloride; Other: diagnostic laboratory biomarker analysis; Drug: capecitabine; Biological: bevacizumab

Detailed Description

OBJECTIVES:

Primary

• Evaluate the objective response (complete and partial) rate in patients with metastatic colorectal adenocarcinoma treated with bevacizumab and modified FOLFIRI 3 chemotherapy.

Secondary

• Determine progression-free and overall survival.
• Determine the tolerance to this regimen.
• Evaluate the resectability rate.
• Evaluate biological markers predictive of the efficacy of this regimen.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1, irinotecan hydrochloride IV over 90 minutes on days 1 and 3, and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

At 14 days after completing chemotherapy, patients with progressive or stable disease receive maintenance therapy comprising bevacizumab and capecitabine.

Biological specimens are collected at baseline and before the fourth course of chemotherapy.

After completion of study therapy, patients are followed every 3 months for 2 years.

• Study Type: Interventional
• Enrollment (Anticipated): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25030
    • Recruiting
    • Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
    • Contact: Christophe Borg, PhD; Phone Number: 33-381-668-705; Email: christophe.borg@efs.sante.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

  • Previously untreated metastatic disease

• Measurable disease by RECIST

  • Must not be located in a prior radiation field
• No cerebral or meningeal metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

• WHO performance status 0-1
• Life expectancy > 12 weeks
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Transaminases ≤ 2 times ULN (5 times ULN if liver metastases present)
• Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases present)
• Creatinine ≤ 130 μmol/L OR creatinine clearance ≥ 30 mL/min
• Proteinuria < 2+ or urine protein ≤ 1 g/24 hours
• Not pregnant or nursing
• Fertile patients of must use effective contraception

Exclusion criteria:

• Uncontrolled cardiac disease
• Prior cerebral vascular accident
• Uncontrolled arterial hypertension
• Severe renal or hepatic insufficiency
• Prior arteriopathy
• Bleeding disorder or nonhealing wound
• Coagulopathy
• Other malignancy within the past 2 years except basal cell or squamous cell skin cancer or curatively treated carcinoma of the cervix
• Psychiatric disorder compromising comprehension or participation in the study
• Intestinal occlusion or subocclusion not caused by medical therapy

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

Exclusion criteria:

• Prior adjuvant bevacizumab or irinotecan hydrochloride
• Concurrent aspirin (> 325 mg/day) or therapeutic anticoagulants
• Surgery in the past 28 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective response (complete and partial) rate

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Overall survival
Tolerance
Resectability rate
Biomarkers predictive of efficacy

Collaborators and Investigators

• Sponsor: Hopital Jean Minjoz
• Investigators: Christophe Borg, PhD, Hopital Jean Minjoz

Publications and helpful links

General Publications

• Jary M, Lecomte T, Bouche O, Kim S, Dobi E, Queiroz L, Ghiringhelli F, Etienne H, Leger J, Godet Y, Balland J, Lakkis Z, Adotevi O, Bonnetain F, Borg C, Vernerey D. Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score. Int J Cancer. 2016 Nov 15;139(10):2325-35. doi: 10.1002/ijc.30367. Epub 2016 Aug 13.

Study record dates

Study Major Dates

• Study Start: April 1, 2007

Study Registration Dates

• First Submitted: October 13, 2007
• First Submitted That Met QC Criteria: October 13, 2007
• First Posted (Estimate): October 16, 2007

Study Record Updates

• Last Update Posted (Estimate): June 27, 2011
• Last Update Submitted That Met QC Criteria: June 23, 2011
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Capecitabine; Bevacizumab; Irinotecan
• Other Study ID Numbers: CDR0000564118; CHRB-Folfiri-III-Avastin; INCA-RECF0432