Study of Cetuximab, Oxaliplatin, 5-FU/LV Versus Oxaliplatin, 5-FU/LV in Patients With Previously Treated Metastatic, EGFR-Positive Colorectal Cancer

A Phase 3 Randomized Multicenter Study of Cetuximab, Oxaliplatin, 5-Fluorouracil, and Leucovorin vs. Oxaliplatin, 5-Fluorouracil, and Leucovorin in Subjects With Previously Treated Metastatic, EGFR-Positive Colorectal Carcinoma

The purpose of this study is to compare overall survival in patients with previously-treated metastatic, epidermal growth factor receptor (EGFR)-positive colorectal cancer treated with oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX4) and cetuximab with FOLFOX4 alone.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: cetuximab; Drug: oxaliplatin; Drug: leucovorin; Drug: 5-fluorouracil; Drug: 5-fluorouracil; Biological: cetuximab

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • ImClone Investigational Site
    • Springdale, Arkansas, United States, 72764
      • ImClone Investigational Site
  • California
    • Fountain Valley, California, United States, 92708
      • ImClone Investigational Site
    • Gilroy, California, United States, 95020
      • ImClone Investigational Site
    • Greenbrae, California, United States, 94904
      • ImClone Investigational Site
    • Orange, California, United States, 92868
      • ImClone Investigational Site
    • Pomona, California, United States, 91767
      • ImClone Investigational Site
    • San Diego, California, United States, 92120
      • ImClone Investigational Site
    • Vista, California, United States, 92083
      • ImClone Investigational Site
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • ImClone Investigational Site
    • Norwalk, Connecticut, United States, 06856
      • ImClone Investigational Site
    • Stamford, Connecticut, United States, 06902
      • ImClone Investigational Site
    • Waterbury, Connecticut, United States, 06708
      • ImClone Investigational Site
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • ImClone Investigational Site
    • Jacksonville, Florida, United States, 32207
      • ImClone Investigational Site
    • Leesburg, Florida, United States, 34748
      • ImClone Investigational Site
    • Orlando, Florida, United States, 32804
      • ImClone Investigational Site
    • Tampa, Florida, United States, 33613
      • ImClone Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • ImClone Investigational Site
    • Macon, Georgia, United States, 31201
      • ImClone Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • ImClone Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • ImClone Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • ImClone Investigational Site
    • Clinton, Maryland, United States, 20735
      • ImClone Investigational Site
  • Michigan
    • St. Joseph, Michigan, United States, 49085
      • ImClone Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • ImClone Investigational Site
    • Rolla, Missouri, United States, 65401
      • ImClone Investigational Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • ImClone Investigational Site
  • New York
    • Armonk, New York, United States, 10504
      • ImClone Investigational Site
    • Brooklyn, New York, United States, 11235
      • ImClone Investigational Site
    • East Setauket, New York, United States, 11733
      • ImClone Investigational Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • ImClone Investigational Site
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • ImClone Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • ImClone Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • ImClone Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • ImClone Investigational Site
    • Nashville, Tennessee, United States, 37203
      • ImClone Investigational Site
  • Utah
    • Ogden, Utah, United States, 84403
      • ImClone Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23230
      • ImClone Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Documented colorectal cancer which is EGFR-positive and is metastatic.
• Prior irinotecan, alone or in combination, as first-line treatment of metastatic disease.

Exclusion Criteria:

• A serious uncontrolled medical disorder that, in the opinion of the Investigator, would impair the ability of the subject to receive protocol therapy.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency.
• Known metastases in the central nervous system.
• Symptomatic sensory or peripheral neuropathy.
• More than one prior chemotherapy regimen for the treatment of metastatic colorectal cancer.
• Prior oxaliplatin therapy.
• Prior cetuximab or other therapy which targets the EGF pathway.
• Prior chimerized or murine monoclonal antibody therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cetuximab+FOLFOX4; Day 1 - cetuximab loading dose of 400 mg/m2 IV, infused over 2 hours; oxaliplatin (85 mg/m2) simultaneously with leucovorin (200 mg/m2), followed by 5-FU 400 mg/m2 IV bolus followed by 5-FU 600 mg/m2 as a 22-hour continuous infusion; Day 2 - leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 IV bolus followed by another dose of 5-FU 600 mg/m2 as a 22-hour continuous infusion; Day 8 - cetuximab maintenance dose of 250 mg/m2 IV infused over 60 minutes	Biological: cetuximab; 400 mg/m2 IV; Other Names: Erbitux™; Drug: oxaliplatin; 85 mg/m2 IV; Other Names: Eloxatin®; Drug: leucovorin; 200 mg/m2 IV; Other Names: Wellcovorin®; Drug: 5-fluorouracil; 400 mg/m2 IV; Other Names: 5-FU; Drug: 5-fluorouracil; 600 mg/m2 IV; Other Names: 5-FU; Biological: cetuximab; 250 mg/m2 IV; Other Names: Erbitux™
Active Comparator: FOLFOX4.; Day 1 - oxaliplatin (85 mg/m2) simultaneously with leucovorin (200 mg/m2), followed by 5-FU 400 mg/m2 IV bolus followed by 5-FU 600 mg/m2 as a 22-hour continuous infusion.; Day 2 - leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 IV bolus followed by another dose of 5-FU 600 mg/m2 as a 22-hour continuous infusion.	Drug: oxaliplatin; 85 mg/m2 IV; Other Names: Eloxatin®; Drug: leucovorin; 200 mg/m2 IV; Other Names: Wellcovorin®; Drug: 5-fluorouracil; 400 mg/m2 IV; Other Names: 5-FU; Drug: 5-fluorouracil; 600 mg/m2 IV; Other Names: 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Compare overall survival in subjects with previously-treated metastatic, epidermal growth factor receptor (EGFR)-positive colorectal cancer treated with oxaliplatin, 5-FU, and LV (FOLFOX4) and cetuximab with FOLFOX4 alone.	Every six weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Compare the response rates between the two treatment arms.	Every six weeks
Compare progression-free survival between the two treatment arms.	Every six weeks
Duration of response within each treatment arm.	Every six weeks
Time to response within each treatment arm.	Every six weeks
Compare the safety profiles between the two treatment arms.	Every six weeks
Compare the quality of life (QOL)between the two treatment arms.	Every six weeks
Conduct an economic assessment comparing healthcare resource utilization between the two treatment arms.	Every six weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Bristol-Myers Squibb

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: June 4, 2003
• First Submitted That Met QC Criteria: June 5, 2003
• First Posted (Estimate): June 6, 2003

Study Record Updates

• Last Update Posted (Estimate): April 12, 2010
• Last Update Submitted That Met QC Criteria: April 8, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Cetuximab
• Other Study ID Numbers: CA225-014