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

March 8, 2004
February 19, 2013
February 2004
November 2012   (final data collection date for primary outcome measure)
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.
Not Provided
Complete list of historical versions of study NCT00079274 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
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

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.

PRIMARY OBJECTIVES:

I. Compare the disease-free survival of patients with curatively resected stage III colon cancer treated with adjuvant irinotecan (irinotecan hydrochloride) vs oxaliplatin with fluorouracil and leucovorin calcium vs both regimens given consecutively (all irinotecan-containing treatment arms are closed to accrual as of 6/1/2005).

II. Compare the disease-free survival of patients treated with these regimens with vs without cetuximab.

SECONDARY OBJECTIVES:

I. Compare the overall survival of patients treated with these regimens. II. Compare the disease-free and overall survival of patients whose tumors express epidermal growth factor receptor treated with these regimens.

III. Compare the toxic effects of these regimens in these patients. IV. Compare the quality of life, measures of patient satisfaction, nutrition, and cancer risk in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to positive lymph node involvement (1-3 vs 4 or more), histology (high [poorly differentiated or undifferentiated] vs low [well to moderately differentiated]), and clinical T stage (T1 or T2 vs T3 vs T4). Patients are randomized to 1 of 6 treatment arms (as of 6/1/2005, patients are randomized to treatment arms I and IV only; arms II, III, V, and VI are closed to accrual).

ARM I: Patients receive oxaliplatin intravenously (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.

ARM II (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive irinotecan hydrochloride 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.

ARM III (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): 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.

ARM IV: 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.

ARM V (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm IV for remainder of therapy): Patients receive cetuximab* as in arm IV and irinotecan hydrochloride, 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.

ARM VI (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm IV for remainder of therapy): Patients receive cetuximab* as in arm IV and chemotherapy as in arm III.

NOTE: *Cetuximab is administered over 2 hours at a higher dose on day 1 of course 1 only.

Quality of life is assessed at baseline, before course 6, and at the end of therapy. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 3 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adenocarcinoma of the Colon
  • Stage III Colon Cancer
  • 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
  • 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.
    Interventions:
    • Drug: oxaliplatin
    • Drug: leucovorin calcium
    • Drug: fluorouracil
  • 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.
    Interventions:
    • Drug: irinotecan hydrochloride
    • Drug: leucovorin calcium
    • Drug: fluorouracil
  • 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.
    Interventions:
    • Drug: irinotecan hydrochloride
    • Drug: oxaliplatin
    • Drug: leucovorin calcium
    • Drug: fluorouracil
  • 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.
    Interventions:
    • Drug: oxaliplatin
    • Drug: leucovorin calcium
    • Drug: fluorouracil
    • Biological: cetuximab
  • 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.
    Interventions:
    • Drug: irinotecan hydrochloride
    • Drug: leucovorin calcium
    • Drug: fluorouracil
    • Biological: cetuximab
  • Experimental: Arm VI (combination chemotherapy, monoclonal antibody)
    Patients receive cetuximab as in arm IV and chemotherapy as in arm III.
    Interventions:
    • Drug: irinotecan hydrochloride
    • Drug: oxaliplatin
    • Drug: leucovorin calcium
    • Drug: fluorouracil
    • Biological: cetuximab

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
3768
Not Provided
November 2012   (final data collection date for primary outcome measure)

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
Both
18 Years to 69 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Puerto Rico
 
NCT00079274
NCI-2009-00639, N0147, U10CA025224, CDR0000355132
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Principal Investigator: Frank Sinicrope North Central Cancer Treatment Group
National Cancer Institute (NCI)
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP