Overview

This trial is active, not recruiting.

Conditions adenocarcinoma of the colon, stage iii colon cancer
Treatments irinotecan hydrochloride, oxaliplatin, leucovorin calcium, fluorouracil, cetuximab
Phase phase 3
Target EGFR
Sponsor National Cancer Institute (NCI)
Collaborator Eastern Cooperative Oncology Group
Start date February 2004
End date November 2012
Trial size 3768 participants
Trial identifier NCT00079274, CDR0000355132, N0147, NCI-2009-00639, NCT00170092, U10CA025224

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
oxaliplatin 1-OHP
Given IV
leucovorin calcium CF
Given IV
fluorouracil 5-fluorouracil
Given IV
(Experimental)
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.
irinotecan hydrochloride Campto
Given IV
leucovorin calcium CF
Given IV
fluorouracil 5-fluorouracil
Given IV
(Experimental)
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.
irinotecan hydrochloride Campto
Given IV
oxaliplatin 1-OHP
Given IV
leucovorin calcium CF
Given IV
fluorouracil 5-fluorouracil
Given IV
(Experimental)
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.
oxaliplatin 1-OHP
Given IV
leucovorin calcium CF
Given IV
fluorouracil 5-fluorouracil
Given IV
cetuximab C225
Given IV
(Experimental)
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.
irinotecan hydrochloride Campto
Given IV
leucovorin calcium CF
Given IV
fluorouracil 5-fluorouracil
Given IV
cetuximab C225
Given IV
(Experimental)
Patients receive cetuximab as in arm IV and chemotherapy as in arm III.
irinotecan hydrochloride Campto
Given IV
oxaliplatin 1-OHP
Given IV
leucovorin calcium CF
Given IV
fluorouracil 5-fluorouracil
Given IV
cetuximab C225
Given IV

Primary Outcomes

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

Secondary Outcomes

Measure
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
Overall survival
time frame: From randomization to death, from any cause, assessed up to 8 years
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

Eligibility Criteria

Male or female participants from 18 years up to 69 years old.

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

Additional Information

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
Principal investigator Frank Sinicrope
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).