Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079274
First received: March 8, 2004
Last updated: February 19, 2013
Last verified: August 2012
  Purpose

This randomized phase III trial is comparing three different combination chemotherapy regimens to see how well they work when given with or without cetuximab in treating patients who have undergone surgery for stage III colon cancer. (As of 6/1/2005, patients will no longer receive irinotecan on this study.) Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with monoclonal antibody therapy and giving them after surgery may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective after surgery in treating colon cancer. (As of 6/1/2005, patients will no longer receive irinotecan on this study.


Condition Intervention Phase
Adenocarcinoma of the Colon
Stage III Colon Cancer
Drug: irinotecan hydrochloride
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Biological: cetuximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) With or Without Cetuximab (C225) After Curative Resection for Patients With Stage III Colon Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival, defined as the time from surgery until the time to tumor recurrence of death, whichever is first [ Time Frame: At 5 years ] [ Designated as safety issue: No ]
    Estimated by the method of Kaplan and Meier.


Secondary Outcome Measures:
  • Comparison of disease free survival between arms [ Time Frame: From surgery until the time to tumor recurrence of death, whichever is first, assessed up to 8 years ] [ Designated as safety issue: No ]
    Estimated by the method of Kaplan and Meier.

  • Overall survival [ Time Frame: From randomization to death, from any cause, assessed up to 8 years ] [ Designated as safety issue: No ]
    Estimated by the method of Kaplan and Meier.

  • Toxicity based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Assessed up to 8 years ] [ Designated as safety issue: Yes ]
    Calculated separately for each drug within a regimen, both by course and over the entire course of therapy.


Estimated Enrollment: 3768
Study Start Date: February 2004
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (combination chemotherapy)
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Experimental: Arm II (combination chemotherapy)
Patients receive irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm I. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Experimental: Arm III (combination chemotherapy)
Patients receive the same treatment as in arm I for 6 courses followed by the same treatment as in arm II for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Experimental: Arm IV (combination chemotherapy, monoclonal antibody)
Patients receive cetuximab IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Experimental: Arm V (combination chemotherapy, monoclonal antibody)
Patients receive cetuximab as in arm IV and irinotecan, leucovorin calcium, and fluorouracil as in arm II. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Experimental: Arm VI (combination chemotherapy, monoclonal antibody)
Patients receive cetuximab as in arm IV and chemotherapy as in arm III.
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the colon

    • Stage III disease
    • No resected stage IV disease
  • No rectal cancer

    • Gross inferior (caudad) margin of the primary tumor must be ≥ 12 cm from the anal verge by rigid proctoscopy
  • Stage III tumor must have been completely resected within the past 56 days

    • Must have documented en bloc resection in patients with tumor adherence to adjacent structures
    • Tumor-related obstructions and colonic perforation are allowed
    • Tumor samples must be available
  • At least 1 pathologically confirmed positive lymph node

    • No evidence of residual involved lymph node disease
  • Synchronous primary colon cancer allowed
  • No distant metastatic disease
  • Performance status - ECOG 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • No uncontrolled high blood pressure
  • No unstable angina
  • No symptomatic congestive heart failure
  • No myocardial infarction with the past 6 months
  • No New York Heart Association class III or IV heart disease
  • No symptomatic pulmonary fibrosis
  • No symptomatic interstitial pneumonitis
  • No prior allergic reaction (known sensitivity) to chimerized or murine monoclonal antibody therapy
  • No known allergy to platinum compounds
  • No documented presence of human anti-mouse antibodies (HAMA)
  • No active uncontrolled bacterial, viral, or systemic fungal infection
  • HIV negative
  • No clinically defined AIDS
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 2 months after study participation
  • No inadequately treated gastrointestinal bleeding
  • No ≥ grade 2 pre-existing peripheral sensory or motor neuropathy
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or lobular carcinoma in situ in 1 breast
  • No other concurrent medical condition that would preclude study participation
  • No concurrent biologic therapy
  • No concurrent oprelvekin
  • No concurrent pegfilgrastim
  • No prior chemotherapy for colon cancer
  • No other concurrent chemotherapy
  • No prior radiotherapy for colon cancer
  • No concurrent targeted agents
  • No prior agents directed against epidermal growth factor-receptor
  • No concurrent ketoconazole or other potent inhibitors of CYP3A4 (e.g., itraconazole or voriconazole)
  • No other concurrent anticancer therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079274

  Show 894 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Frank Sinicrope North Central Cancer Treatment Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079274     History of Changes
Obsolete Identifiers: NCT00170092
Other Study ID Numbers: NCI-2009-00639, N0147, U10CA025224, CDR0000355132
Study First Received: March 8, 2004
Last Updated: February 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Fluorouracil
Oxaliplatin
Irinotecan
Cetuximab
Camptothecin
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014