RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving the drugs in different combinations may kill more tumor cells. It is not yet known whether receiving irinotecan with fluorouracil and leucovorin is more effective than receiving oxaliplatin with fluorouracil and leucovorin in treating recurrent metastatic colorectal cancer

PURPOSE: Randomized phase III trial to compare the effectiveness of irinotecan with oxaliplatin followed by fluorouracil and leucovorin in treating patients with recurrent metastatic colorectal cancer.

Condition	Treatment or Intervention	Phase
recurrent colon cancer adenocarcinoma of the rectum Stage IV rectal cancer recurrent rectal cancer stage IV colon cancer adenocarcinoma of the colon	Drug: fluorouracil  Drug: irinotecan  Drug: leucovorin calcium  Drug: oxaliplatin	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the efficacy of leucovorin calcium plus fluorouracil with either irinotecan or oxaliplatin in terms of progression free survival in patients with recurrent metastatic colorectal cancer.

II. Compare the efficacy, tolerance, quality of life, and overall survival in this patient population.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating institution and measurable or evaluable disease.

Patients are randomized to receive either a 2 hour continuous infusion of irinotecan or a 2 hour continuous infusion of oxaliplatin on day 1. All patients receive a 2 hour continuous infusion of leucovorin calcium followed by IV bolus and 48 hour continuous infusion of fluorouracil on days 1 and 2. Courses are repeated every 2 weeks.

Patients will receive the alternate treatment if disease progression or unacceptable toxicity occurs on their initial treatment.

Patients are followed every 3 months after end of treatment.

PROJECTED ACCRUAL: This study will accrue a total of 109 patients per arm over approximately 18 months.

Ages Eligible for Study:  18 Years   -   75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven recurrent stage IV adenocarcinoma of the colon and rectum
• No CNS metastases
• Bidimensionally measurable lesion (at least 2 cm in dimension) or evaluable disease (as malignant ascites or bone metastases) as documented by CT or MRI; Must be outside prior radiotherapy field

--Prior/Concurrent Therapy--

• Biologic therapy: No prior immunotherapy for metastatic disease
• Chemotherapy: No prior chemotherapy for metastatic disease; At least 6 months since prior adjuvant chemotherapy with no disease progression or after metastatic liver resection; No prior chemotherapy with oxaliplatin or irinotecan
• Endocrine therapy: Not specified
• Radiotherapy: At least 2 weeks since prior radiotherapy
• Surgery: At least 2 weeks since surgery
• Other: At least 30 days since use of investigational agent

--Patient Characteristics--

• Age: 18 to 75
• Performance status: WHO 0-2
• Life expectancy: Greater than 3 months
• Hematopoietic: Absolute neutrophil count greater than 1,500/mm3; Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 times normal; Alkaline phosphatase no greater than 3 times normal; SGOT/SGPT no greater than 3 times normal
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No uncontrolled congestive heart failure or angina pectoris in the past 6 months; No hypertension or arrhythmia in the past 6 months
• Neurologic: No peripheral neuropathy; No significant neurologic or psychiatric disorder
• Other: No complete or partial obstruction of the bowel; No serious nonmalignant disease; No active infection; No second malignancy except in situ cervical carcinoma or nonmelanomatous skin carcinoma; No chronic diarrhea; Not pregnant or nursing; Fertile women must use adequate contraception

France
      Hopital Saint Antoine, Paris,  75571,  France

Study chairs or principal investigators

Aimery De Gramont,  Study Chair,  Federation Nationale des Centres de Lutte Contre le Cancer   

Study ID Numbers:  CDR0000066151; FRE-GERCOR-C97-3/CPTF308; FRE-C97-3/CPTF308; EU-97044; FRE-C97-3/CPTF301; RP-FRE-C97-3/CPTF308
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003260
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08