Cetuximab and Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer

Phase 2 Study to Improve Tolerance of Chemotherapy Involving Cetuximab and Multidrug FOLFIRI, With Pharmacokinetic and Pharmacogenetic Studies, in Patients With Metastatic Colorectal Cancer

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, such as irinotecan, fluorouracil, and leucovorin, 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 in treating patients with advanced or metastatic colorectal cancer.

Study Overview

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

Detailed Description

OBJECTIVES:

Primary

• Improve hematologic and gastrointestinal tolerance to cetuximab and irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with advanced or metastatic colorectal cancer.

Secondary

• Increase the effectiveness of this regimen by intensifying the treatment.
• Specify the constitutional genetic and genomic tumor parameters that could interfere with and predict the toxicity and/or antitumor efficacy of this regimen.
• Assess the time to progression.

OUTLINE: This is a multicenter study.

Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and cetuximab IV over 1-2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Pharmacokinetic and pharmacogenetic studies are also conducted.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49036
    • Centre Paul Papin

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 colorectal cancer

  • Advanced or metastatic disease
• Scheduled to receive first- or second-line therapy for metastatic disease
• No cerebral metastases or symptomatic or uncontrolled meningeal disease

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• ANC ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No intestinal blockage
• No complete dihydropyrimidine dehydrogenase deficiency
• No chronic inflammatory disease of the colon
• No other cancer except for nonmelanoma skin cancer or curatively treated carcinoma of the cervix or breast

• No other severe condition, or condition that is likely to worsen, including any of the following:

  • Unstable heart disease
  • Myocardial infarction within the past 6 months
  • Active uncontrolled infection
• No contraindication to atropine

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior anticancer therapy
• More than 4 weeks since prior and no other concurrent investigational therapy
• Prior adjuvant chemotherapy allowed
• No prior fluorouracil or irinotecan hydrochloride
• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Improvement of hematologic and gastrointestinal tolerance to therapy

Secondary Outcome Measures

Outcome Measure
Time to progression
Efficacy
Genetic and genomic tumor parameters that could interfere with and predict the toxicity and/or antitumor efficacy of therapy

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest
• Investigators: Study Chair: Erick Gamelin, MD, Institut Cancerologie de l'Ouest

Publications and helpful links

General Publications

• Rouits E, Charasson V, Petain A, Boisdron-Celle M, Delord JP, Fonck M, Laurand A, Poirier AL, Morel A, Chatelut E, Robert J, Gamelin E. Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients. Br J Cancer. 2008 Oct 21;99(8):1239-45. doi: 10.1038/sj.bjc.6604673. Epub 2008 Sep 16.
• Rollin J, Payance A, Gouilleux-Gruart V, Boisdron-Celle M, Azzopardi N, Morel A, Gruel Y, Paintaud G, Gamelin E, Watier H, Lecomte T. Significant effect of VEGFA polymorphisms on the clinical outcome of metastatic colorectal cancer patients treated with FOLFIRI-cetuximab. Pharmacogenomics. 2015 Dec;16(18):2035-43. doi: 10.2217/pgs.15.139. Epub 2015 Nov 30.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 15, 2007
• First Posted (Estimate): November 16, 2007

Study Record Updates

• Last Update Posted (Estimate): May 13, 2011
• Last Update Submitted That Met QC Criteria: May 12, 2011
• Last Verified: May 1, 2011

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; Leucovorin; Irinotecan; Calcium; Levoleucovorin; Cetuximab
• Other Study ID Numbers: CDR0000574065; CPP-FOLFIRICETUX; INCA-RECF0108