RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more tumor cells.

PURPOSE: Phase II trial to compare the effectiveness of either irinotecan or fluorouracil plus leucovorin in treating patients who have metastatic colorectal cancer that has been previously treated with oxaliplatin with or without irinotecan.

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

Further Study Details: 

OBJECTIVES:

• Determine the tumor response rate in patients receiving irinotecan or fluorouracil and leucovorin calcium for metastatic colorectal cancer previously treated with oxaliplatin with or without irinotecan.
• Determine the time to tumor progression, time to treatment failure, and overall survival of patients treated with these regimens.
• Determine the toxic effects of these regimens in these patients.
• Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (oxaliplatin-based therapy vs irinotecan and oxaliplatin combination therapy). Patients are assigned to one of two treatment arms.

• Arm I (prior oxaliplatin-based chemotherapy): Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks.
• Arm II (prior irinotecan and oxaliplatin combination chemotherapy): Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously on days 1 and 2. Treatment repeats every 2 weeks.
• Both arms: Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with a confirmed complete response for 2 consecutive courses may discontinue treatment at investigator's discretion. Quality of life is assessed at baseline, approximately every 6 weeks during treatment, and then after the last course of treatment.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 40-80 patients (20-40 per arm) will be accrued for this study within 1-2 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic colorectal adenocarcinoma incurable by surgery or not amenable to radiotherapy with curative intent
• Progressive disease after one of the following prior treatments for metastatic disease:
• Oxaliplatin-based chemotherapy
• Irinotecan and oxaliplatin combination chemotherapy
• At least 1 measurable lesion
• At least 20 mm in at least one dimension
• No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 0.5 mg/dL above upper limit of normal (ULN)
• AST no greater than 5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No unstable angina
• No symptomatic congestive heart failure
• No serious uncontrolled cardiac arrhythmia

Other:

• No active or uncontrolled infection
• No evidence of other serious illness
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No concurrent sargramostim (GM-CSF)

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No more than 1 prior chemotherapy regimen for advanced colorectal cancer
• Prior adjuvant chemotherapy allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to more than 25% of bone marrow

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior major surgery

Arizona
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Florida
      Mayo Clinic, Jacksonville,  Florida,  32224,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68106,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States
Canada, Saskatchewan
      Allan Blair Cancer Centre, Regina,  Saskatchewan,  S4T 7T1,  Canada

Study chairs or principal investigators

Henry Clement Pitot, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000068635; NCCTG-N0048
Record last reviewed:  April 2003
Last Updated:  October 13, 2004
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00016952
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08