RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, capecitabine, fluorouracil, and leucovorin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery (adjuvant therapy) may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating resected stage III colon cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two adjuvant combination chemotherapy regimens in treating chemotherapy-naïve (not previously treated with chemotherapy) patients who have undergone resection for stage III colon cancer.

Condition	Treatment or Intervention	Phase
stage III colon cancer	Drug: capecitabine  Drug: fluorouracil  Drug: leucovorin calcium  Drug: oxaliplatin  Procedure: adjuvant therapy  Procedure: chemotherapy	Phase III

OBJECTIVES: Primary

• Compare disease-free survival of chemotherapy-naïve patients with resected stage III colon cancer treated with adjuvant oxaliplatin and capecitabine vs fluorouracil and leucovorin calcium.

Secondary

• Compare overall survival of patients treated with these regimens.
• Compare safety profiles of these regimens in these patients.
• Compare the perceived treatment convenience and satisfaction in patients treated with these regimens.
• Compare medical care utilization in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to number of positive lymph nodes (3 or less vs 4 or more), baseline carcinoembryonic antigen level (normal vs abnormal), geographic region, interaction between lymph nodes and geographic region, and regimen used in arm II (regimen A [Mayo Clinic] vs regimen B [Roswell Park]). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral capecitabine twice daily on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for a total of 8 courses.
• Patients receive 1 of the following regimens, depending on participating center:
• Regimen A (Mayo Clinic regimen): Patients receive leucovorin calcium IV and fluorouracil IV on days 1-5. Treatment repeats every 28 days for 6 courses.
• Regimen B (Roswell Park regimen): Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 4 courses. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 3 years, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,850 patients (925 per treatment arm) will be accrued for this study within 1.5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III colon cancer
• Tumor located at least 15 cm from the anal verge by endoscopy OR located above the peritoneal reflection as assessed during surgery
• At least 1 positive lymph node
• Surgery with curative intent performed within the past 8 weeks
• No macroscopic or microscopic evidence of remaining tumor
• No requirement for neoadjuvant and/or adjuvant radiotherapy
• No evidence of metastatic disease, including presence of tumor cells in ascites
• Cytokeratin-positive cells in bone marrow is not considered metastatic disease

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 5 years

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine clearance > 50 mL/min OR
• Creatinine ≤ ULN

Cardiovascular

• No clinically significant, active cardiac disease
• No symptomatic coronary artery disease
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No myocardial infarction within the past year

Pulmonary

• No interstitial pneumonia
• No extensive symptomatic fibrosis of the lungs

Gastrointestinal

• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome

Neurologic

• No uncontrolled seizures
• No CNS disorders
• No grade 1 or greater peripheral neuropathy
• Absence of deep tendon reflexes as the sole neurologic abnormality allowed

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except cured basal cell skin cancer or carcinoma in situ of the cervix
• No clinically significant psychiatric disability that would preclude giving informed consent or complying with study treatment
• No known dihydropyrimidine dehydrogenase deficiency
• No concurrent serious uncontrolled infection
• No other serious uncontrolled disease
• No known hypersensitivity to platinum compounds or any study medications

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for colon cancer
• No concurrent active or passive immunotherapy

Chemotherapy

• No prior cytotoxic chemotherapy for colon cancer

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• No prior radiotherapy for colon cancer
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery
• No prior organ allograft

Other

• More than 4 weeks since prior investigational drugs, agents, or procedures
• No concurrent sorivudine or its chemically related analogues (e.g., brivudine)
• No other concurrent cytotoxic agents
• No other concurrent investigational drugs
• No concurrent cold cap for prevention of alopecia OR iced mouth rinses for stomatitis (arm I)

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-7187,  United States; Recruiting

Study chairs or principal investigators

Joel Randolph Hecht, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000355119; UCLA-0310023; ROCHE-NO16968
Record last reviewed:  February 2004
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00080691
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-10