Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. Compare the disease-free survival of patients with curatively resected stage III colon cancer treated with adjuvant irinotecan 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).
2. Compare the disease-free survival of patients treated with these regimens with vs without cetuximab.

Secondary

1. Compare the overall survival of patients treated with these regimens.
2. Compare the disease-free and overall survival of patients whose tumors express epidermal growth factor receptor treated with these regimens.
3. Compare the toxic effects of these regimens in these patients.
4. Compare the quality of life, measures of patient satisfaction, nutrition, and cancer risk in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent biologic therapy
• No concurrent oprelvekin
• No concurrent pegfilgrastim

Chemotherapy

• No prior chemotherapy for colon cancer
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for colon cancer

Surgery

• See Disease Characteristics

Other

• 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
• No concurrent targeted agents

Patient Characteristics:

Age

• 18 to 69

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• 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

Pulmonary

• No symptomatic pulmonary fibrosis
• No symptomatic interstitial pneumonitis

Immunologic

• 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

Other

• 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

Expected Enrollment

A total of 3,768 patients will be accrued for this study.

Outcomes

Disease-free survival at 3 years

Overall survival

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 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 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, 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.

Huang J, Sargent DJ, Mahoney MR, et al.: Pilot experience with adjuvant FOLFIRI with or without cetuximab in patients with resected stage III colon cancer: NCCTG Intergroup N0147. [Abstract] J Clin Oncol 29 (Suppl 15): A-3522, 2011.

Alberts, SR, Sargent DJ, Smyrk TC, et al.: Adjuvant mFOLFOX6 with or without cetuxiumab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): results from NCCTG Intergroup Phase III Trial N0147. [Abstract] J Clin Oncol 28 (Suppl 18): A-CRA3507, 2010.

Goldberg RM, Sargent DJ, Thibodeau SN, et al.: Adjuvant mFOLFOX6 plus or minus cetuximab (Cmab) in patients (pts) with KRAS mutant (m) resected stage III colon cancer (CC): NCCTG Intergroup Phase III Trial N0147. [Abstract] J Clin Oncol 28 (Suppl 15): A-3508, 2010.

Jatoi A, Green EM, Rowland KM Jr, et al.: Clinical predictors of severe cetuximab-induced rash: observations from 933 patients enrolled in north central cancer treatment group study N0147. Oncology 77 (2): 120-3, 2009.[PUBMED Abstract]

Sloan JA, Mahoney MR, Sargent DJ, et al.: Was it worth it (WIWI)? Patient satisfaction with clinical trial participation: results from North Central Cancer Treatment Group (NCCTG) phase III trial N0147. [Abstract] J Clin Oncol 29 (Suppl 15): A-6122, 2011.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Steven Alberts, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Albert Bernath, MD, Protocol co-chair		Ph: 570-214-9290
Frank Sinicrope, MD, Principal investigator		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Eastern Cooperative Oncology Group

Emily Chan, MD, PhD, Protocol co-chair		Ph: 615-322-4967; 800-811-8480 Email: emily.chan@vanderbilt.edu

Related Information

Featured trial article

Registry 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
Trial Start Date		2004-02-10
Trial Completion Date		2011-11-11
Registered in ClinicalTrials.gov		NCT00079274
Date Submitted to PDQ		2004-01-29
Information Last Verified		2009-11-26
NCI Grant/Contract Number		CA25224

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