Cetuximab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

Phase II Study Evaluating the Efficacy and Safety of cétuximab Associated With the Protocol FOLFIRINOX (LV5FU Simplified Combined With Irinotecan and Oxaliplatin) in the First Line Treatment in Patients With Metastatic Colorectal Cancer Expressing EGFR or Not

RATIONALE: Monoclonal antibodies, such as cetuximab, 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 cetuximab together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy works as first-line therapy in treating patients with metastatic colorectal cancer.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: oxaliplatin; Biological: cetuximab

Detailed Description

OBJECTIVES:

Primary

• Determine the complete response rate in patients with metastatic colorectal cancer treated with cetuximab and FOLFIRINOX chemotherapy comprising oxaliplatin, irinotecan hydrochloride, leucovorin calcium, and fluorouracil as first-line therapy.

Secondary

• Determine the objective response rate in patients treated with this regimen.
• Assess the tolerability of this regimen in these patients.
• Determine the time to response and time to progression in patients treated with this regimen.
• Determine the survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive cetuximab IV over 1-2 hours on days 1 and 8. Patients also receive FOLFIRINOX chemotherapy comprising oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 30-90 minutes, 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 15 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer

  • Metastatic, unresectable disease
• May or may not express the EGFR gene

• Measurable disease, defined as ≥ 1 measurable lesion by MRI or CT scan

  • Lesion must be outside an irradiated area

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Life expectancy > 3 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Transaminases ≤ 2.5 times ULN (5 times ULN if hepatic metastases are present)
• Creatinine ≤ 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No peripheral or symptomatic neuropathy ≥ grade 2 (NCI-CTCAE)
• No complete or partial intestinal blockage
• No intestinal inflammatory disease (e.g., Crohn's disease or ulcerative colitis)
• No chronic diarrhea
• No severe unstable cardiac disease (despite treatment)
• No myocardial infarction within the past 6 months
• No neurological or psychiatric illness, including epilepsy or dementia
• No uncontrolled active infection
• No other prior or concurrent malignancy within the past 5 years except for curatively treated basal cell skin cancer
• No psychological, familial, social, or geographic reason that would preclude study follow-up

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy for metastatic disease

  • Prior fluorouracil-based adjuvant chemotherapy allowed provided it was administered ≥ 4 weeks ago
• At least 4 weeks since prior and no other concurrent experimental therapy
• No prior irinotecan hydrochloride, oxaliplatin, or monoclonal antibody
• No prior intestinal resection (e.g., hemicolectomy or extended resection of the small intestine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ERBIRINOX; 5FU + Irinotecan + Oxaliplatine + Cetuximab	Drug: fluorouracil; Drug: leucovorin calcium; Drug: irinotecan hydrochloride; Drug: oxaliplatin; Biological: cetuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response rate	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival	6 months
Objective response rate	6 months
Time to progression	6 months
Adverse events by using NCI-CTC	6 months
Time to response	6 months

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Investigators: Study Chair: Marc Ychou, MD, PhD, Institut du Cancer de Montpellier - Val d'Aurelle

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): November 17, 2011

Study Registration Dates

• First Submitted: November 9, 2007
• First Submitted That Met QC Criteria: November 9, 2007
• First Posted (Estimate): November 12, 2007

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer
• 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; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Calcium; Levoleucovorin; Cetuximab
• Other Study ID Numbers: CDR0000574149; CLCC-ERBIRINOX; INCA-RECF0288; EUDRACT-2005-004746-13; MERCK-CLCC-ERBIRINOX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No