RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. SU5416 may stop the growth of tumor cells by stopping blood flow to the tumor. It is not yet known whether combination chemotherapy will be more effective with or without SU5416 in treating metastatic colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without SU5416 in treating patients who have 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 Quality of Life adenocarcinoma of the colon	Drug: fluorouracil  Drug: irinotecan  Drug: leucovorin calcium  Drug: SU5416	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the survival of patients with previously untreated metastatic colorectal cancer treated with fluorouracil, leucovorin calcium, and irinotecan with or without SU5416. II. Compare the antitumor efficacy of these regimens in these patients. III. Evaluate the additional measures of clinical benefit in patients treated with these regimens. IV. Determine the relative safety profile of these regimens in these patients. V. Assess quality of life of patients treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1), baseline lactate dehydrogenase (normal vs elevated), and treatment regimen. Patients are randomized to 1 of 2 treatment arms by 2 different regimens (Saltz vs de Gramont). Regimen I (Saltz): Arm IA: Patients receive SU5416 IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, and 39. Patients also receive irinotecan IV over 30-90 minutes, leucovorin calcium IV over 5-10 minutes, and fluorouracil IV over 5-10 minutes on days 1, 8, 15, and 22. Arm IIA: Patients receive irinotecan, leucovorin calcium, and fluorouracil as in arm I. Treatment in both arms repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Regimen II (de Gramont): Arm IB: Patients receive SU5416 as in arm IA. Patients also receive irinotecan IV over 30-90 minutes on days 1, 15, and 29 and leucovorin calcium IV over 2 hours and fluorouracil IV over 2 hours on days 1, 2, 15, 16, 29, and 30. Arm IIB: Patients receive irinotecan, leucovorin calcium, and fluorouracil as in arm IB. Treatment in both arms repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at the beginning of each course, and then at the end of treatment. Patients are followed at 1 month and then every 2 months for 4 years.

PROJECTED ACCRUAL: A total of 1,270 patients (635 per treatment arm) will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed adenocarcinoma of the colon or rectum; Newly diagnosed or recurrent disease
• Measurable or evaluable metastatic disease that is previously untreated
• No known brain or leptomeningeal metastases

--Prior/Concurrent Therapy--

• Biologic therapy: At least 6 months since prior adjuvant antibody therapy, immunotherapy, gene therapy, vaccine therapy, or cytokine therapy; No prior systemic biologic therapy for metastatic disease, including antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, or angiogenesis inhibitors (e.g., SU5416, matrix metalloprotease inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody); No concurrent antibody therapy, immunotherapy, gene therapy, vaccine therapy, or angiogenesis inhibitors; No concurrent sargramostim (GM-CSF)
• Chemotherapy: At least 6 months since prior adjuvant chemotherapy (e.g., fluorouracil, leucovorin calcium, levamisole, irinotecan, oxaliplatin, capecitabine, fluorouracil-uracil, or other cytotoxic agents); No prior systemic chemotherapy for metastatic disease; No prior intra-arterial cytotoxic chemotherapy for metastatic disease; No other concurrent chemotherapy
• Endocrine therapy: No concurrent anticancer hormonal therapy
• Radiotherapy: At least 6 months since prior adjuvant radioimmunotherapy or radiotherapy and recovered; No concurrent radiotherapy
• Surgery: Recovered from prior surgery
• Other: At least 6 months since other prior adjuvant therapy; No other prior systemic anticancer therapy for metastatic disease; No other concurrent anticancer therapy; No other concurrent experimental drugs; No concurrent participation in another clinical trial

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 8.0 g/dL
• Hepatic: Bilirubin no greater than 1.8 times upper limit of normal (ULN); SGOT no greater than 5 times ULN; Alkaline phosphatase no greater than 5 times ULN; Lactate dehydrogenase no greater than 5 times ULN
• Renal: Creatinine no greater than 1.5 times ULN
• Cardiovascular: No myocardial infarction within the past 6 months; No ongoing unstable angina; No symptomatic congestive heart failure; No serious uncontrolled cardiac dysrhythmia; No stroke within the past 6 months
• Gastrointestinal: No active inflammatory bowel disease; No significant bowel obstruction; No chronic diarrhea grade 2 or greater
• Other: HIV negative; No AIDS-related illness; No known allergy to Cremaphor-containing products, irinotecan, fluorouracil, or to both warfarin (or similar oral anticoagulants) and low-molecular weight heparin; No other malignancy within the past 5 years except nonmelanoma skin cancer; No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States

Study chairs or principal investigators

Lee S. Rosen,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068766; UCLA-001003701; NCI-G01-1980; SUGEN-SU5416.035
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  July 11, 2001
ClinicalTrials.gov Identifier:  NCT00021281
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08