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 may kill more tumor cells. It is not yet known which treatment regimen is more effective for colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of immediate with delayed fluorouracil plus leucovorin in treating patients with advanced colorectal cancer without signs or symptoms of disease.

Condition	Treatment or Intervention	Phase
recurrent colon cancer stage III colon cancer stage III rectal cancer Stage IV rectal cancer recurrent rectal cancer stage IV colon cancer	Drug: fluorouracil  Drug: leucovorin calcium	Phase III

Further Study Details: 

OBJECTIVES: I. Compare survival and quality of life in asymptomatic patients with advanced colorectal cancer randomized to immediate fluorouracil/leucovorin (5-FU/CF) vs. 5-FU/CF delayed until onset of symptoms.

PROTOCOL OUTLINE: Randomized, unblinded study.

Arm I: Single-Agent Chemotherapy with Drug Modulation. Fluorouracil, 5-FU, NSC-19893; with Leucovorin calcium, CF, NSC-3590.

Arm II: Observation followed by Single-Agent Chemotherapy with Drug Modulation. Clinical observation until symptomatic; followed by 5-FU; with CF.

PROJECTED ACCRUAL: 144 patients will be entered over 4 years.

Ages Eligible for Study:  18 Years   -   79 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically confirmed cancer of the colon or rectum that is locally advanced or metastatic; Primary lesion was or is located in the large bowel as confirmed by endoscopy, radiology, or surgery; Radiologic or clinical evidence of metastasis subsequent to resection does not require histologic or cytologic confirmation unless: Interval between primary surgery and development of metastasis is greater than 5 years OR Primary cancer was Dukes' A or B1
• Ineligible for potentially curative therapy, e.g.: Surgical resection of a limited hepatic or pulmonary metastasis; Irradiation of locally recurrent colon or rectal cancer
• No or minimal symptoms related to the cancer, i.e.: No persistent pain requiring regular narcotic analgesia; No persistent fever greater than 38 degrees C; No symptomatic bowel obstruction; No persistent nausea requiring medication; No weight loss of greater than 5 kg over the previous 3 months unless clearly not associated with the cancer (e.g., associated with surgery or intercurrent illness)
• Symptomatic relapse/metastases rendered asymptomatic by secondary surgery or radiotherapy are eligible provided the patient remains asymptomatic for at least 6 weeks following such treatment
• No CNS metastases
• No significant ascites, pleural effusion, or pericardial effusion

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for metastatic disease or local recurrence; Prior fluorouracil-based or other adjuvant therapy allowed; At least 6 months required between completion of therapy and documentation of metastasis or recurrence
• Endocrine therapy: Not specified
• Radiotherapy: Prior radiotherapy allowed
• Surgery: Prior surgery allowed

--Patient Characteristics--

• Age: Adult under 80 (i.e., of legal age to sign own informed consent according to institutional policy)
• Performance status: Karnofsky 90-100%; ECOG 0
• Hematopoietic: Granulocytes at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than upper limit of normal
• Renal: Creatinine less than 2.26 mg/dL
• Cardiovascular: No arrhythmia
• Other: No infection; No other medical condition that is uncontrolled or could be aggravated by the protocol therapy; No prior or concurrent second cancer except: Nonmelanomatous skin cancer; In situ cervical cancer; No pregnant women; Adequate contraception required of fertile patients
• Blood/body fluid analyses to determine eligibility and quality-of-life questionnaire completed within 14 days prior to randomization; imaging studies of sites of disease completed within 28 days prior to randomization

Arizona
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  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,  10309-1016,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      CentraCare Clinic, Saint Cloud,  Minnesota,  56303,  United States
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
North Dakota
      Altru Health Systems, Grand Forks,  North Dakota,  58201,  United States
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
      Quain & Ramstad Clinic, P.C., Bismarck,  North Dakota,  58501,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57105-1080,  United States
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States

Study chairs or principal investigators

Malcolm J. Moore,  Study Chair,  National Cancer Institute of Canada   
Henry Clement Pitot,  Study Chair

Study ID Numbers:  CDR0000063607; CAN-NCIC-CO10; NCI-V94-0463; NCCTG-JCO.10
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002570
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08