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 combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy consisting of fluorouracil - uracil and leucovorin plus radiation therapy in treating patients with colorectal cancer who have undergone surgery to remove the tumor.

Condition	Treatment or Intervention	Phase
stage III rectal cancer stage I rectal cancer stage II colon cancer stage II rectal cancer stage III colon cancer	Procedure: chemotherapy  Procedure: radiation therapy  Drug: drug modulation  Drug: fluorouracil-uracil  Drug: leucovorin calcium	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of postoperative fluorouracil-uracil plus leucovorin calcium concurrently with radiotherapy in patients with colorectal cancer. II. Determine the toxicity of this regimen in these patients. III. Determine the response of tumors in patients with measurable disease treated with this regimen.

PROTOCOL OUTLINE: This is a dose-escalation study of fluorouracil-uracil (UFT). Beginning within 10 weeks after definitive surgery, patients receive oral UFT and oral leucovorin calcium (CF) 3 times a day on days 1-28. Treatment continues every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of the second course, patients undergo radiotherapy to the tumor bed and involved lymph nodes 5 days a week for 5 weeks, followed by boost radiotherapy to the primary tumor bed for 5-16 days. Patients receive 3 additional courses of UFT plus CF beginning 4 weeks after completion of radiotherapy or after recovery from the toxic effects of UFT, whichever occurs later. Patients who have measurable disease with ongoing response after the fifth course receive additional courses of UFT and CF. Cohorts of 3-6 patients receive escalating doses of UFT during the second course until the maximum tolerated dose (MTD) is determined. The MTD is defined as highest dose at which the minority of patients experience dose-limiting toxicity. Patients are followed every 3 months for 1 year and then at the discretion of the investigator.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of colorectal cancer for which postoperative radiotherapy to the pelvis is indicated

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent antineoplastic biological response modifiers
• Chemotherapy: No prior systemic chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; No prior radiotherapy to the pelvis
• Surgery: See Disease Characteristics
• Other: No other concurrent investigational drugs; No other concurrent antineoplastic therapy; No concurrent halogenated antiviral agent (e.g., sorivudine)

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 3 months
• Hematopoietic: WBC at least 4,000/mm3; Absolute granulocyte count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; ALT no greater than 1.25 times upper limit of normal (ULN) (no greater than 5 times ULN if elevation secondary to malignancy); Alkaline phosphatase no greater than 1.25 times ULN (no greater than 5 times ULN if elevation secondary to malignancy)
• Renal: Creatinine normal OR Creatinine clearance normal or greater than 60 mL/min
• Other: No medical or psychiatric condition that would preclude study; No prior malignancy except: Appropriately treated localized epithelial skin or cervical cancer; Remote history of other cured malignancy (at the discretion of the sponsor); Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Bruce David Minsky,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000064898; MSKCC-96025; NCI-V96-0942; BMS-MSKCC-96025
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002801
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08