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 colorectal cancer by stopping blood flow to the tumor. It is not yet known whether chemotherapy is more effective with or without SU5416 in treating metastatic colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of leucovorin and fluorouracil with or without SU5416 in treating patients who have metastatic colorectal cancer.

Condition	Treatment or Intervention	Phase
recurrent colon cancer Stage IV rectal cancer recurrent rectal cancer stage IV colon cancer Quality of Life adenocarcinoma of the colon	Drug: fluorouracil  Drug: leucovorin calcium  Drug: SU5416	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the median survival in patients with metastatic colorectal cancer treated with fluorouracil and leucovorin calcium with or without SU5416. II. Compare the time to progression, duration of response, and objective response in these patients on these two regimens. III. Compare the percentage 6 month, 9 month, and one year survival of these patients on these two regimens. IV. Compare the time to treatment failure in these patients on these two regimens. V. Determine the health related quality of life of these patients on these two regimens. VI. Compare the palliative and biologic effects of SU5416 in these patients. VII. Determine the safety and tolerability of fluorouracil and leucovorin calcium plus SU5416 in these patients.

PROTOCOL OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to performance status (ECOG 0 vs 1), site of primary disease (colon vs rectum), measurable or evaluable disease, and prior fluorouracil adjuvant chemotherapy (none vs at least 1 dose). Patients are randomized to one of two treatment arms: Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV bolus 1 hour into leucovorin calcium administration weekly for 6 weeks. Arm II: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV bolus 1 hour into leucovorin calcium administration weekly for 6 weeks, plus SU5416 twice weekly for 8 weeks. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed prior to study, at weeks 4 and 8 of each course, and then post study. Patients are followed post study at one month and then every 2 months until death.

PROJECTED ACCRUAL: A total of 710 patients (355 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed, newly diagnosed or recurrent, metastatic colorectal cancer; Primary disease was adenocarcinoma of the colon or rectum
• Bidimensionally measurable or evaluable disease
• No CNS metastases

--Prior/Concurrent Therapy--

• Biologic therapy: No prior immunotherapy, vaccine therapy, cytokine therapy, or biologic therapy for metastatic disease; No prior angiogenesis inhibition therapy (e.g., metalloproteinase inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody therapy or other experimental drugs acting directly on the VEGF/Flk-1 signaling pathway); Prior antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, or radioimmunotherapy allowed in adjuvant setting only Concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF) allowed for anemia, neutropenia, or thrombocytopenia; No concurrent immunotherapy
• Chemotherapy: No prior systemic chemotherapy for metastatic disease; No prior intra-arterial cytotoxic chemotherapy; No more than one prior course of fluorouracil based adjuvant therapy (e.g., intravenous fluorouracil or capecitabine) with the last dose administered at least 6 months ago; No prior SU5416; No other concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: At least 2 weeks since prior radiotherapy; Concurrent localized palliative radiotherapy allowed unless indicative of disease progression
• Surgery: At least 4 weeks since prior major surgery (not including surgical placement of a venous access device); Prior surgical resection of hepatic metastases allowed
• Other: No prior investigational therapy for metastatic disease; No other concurrent investigational agents

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1
• Life expectancy: At least 12 weeks
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 75,000/mm3; Hemoglobin at least 8 g/dL
• Hepatic: Bilirubin no greater than 2.2 mg/dL; AST no greater than 5 times upper limit of normal
• Renal: Creatinine no greater than 2.0 mg/dL; Creatinine clearance at least 50 mL/min
• Other: Not pregnant; Negative pregnancy test; Fertile patients must use effective contraception; No known allergy to Cremophor or Cremophor based drug products; No uncontrolled colon or small bowel disorders; No other malignancy within the past 5 years, except: Basal cell skin cancer; Carcinoma in situ of the cervix; No other acute or chronic medical or psychiatric condition, or laboratory abnormality that would preclude compliance

Alabama
      Alabama Oncology, LLC, Montgomery,  Alabama,  36106-2801,  United States
California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Office of Richard Shapiro, Benjamin Stafford, and Sharon J. Yee, Arcadia,  California,  91007-7678,  United States
      Scripps Clinic, La Jolla,  California,  92037,  United States
      St. Francis Hospital, San Francisco,  California,  94109,  United States
      Tower Hematology Oncology Medical Group, Los Angeles,  California,  90048,  United States
Florida
      Comprehensive Cancer Care Specialists of Boca Raton, Boca Raton,  Florida,  33428,  United States
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612,  United States
Hawaii
      Queen's Medical Center, Honolulu,  Hawaii,  96813,  United States
Louisiana
      Mary Bird Perkins Cancer Center, Baton Rouge,  Louisiana,  70809,  United States
Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21231,  United States
Massachusetts
      Cancer Center of Boston, Boston,  Massachusetts,  02120,  United States
Michigan
      Michigan State University, East Lansing,  Michigan,  48824,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
New Jersey
      APN-IMPATH Research Corporation, Fort Lee,  New Jersey,  07024,  United States
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
New York
      New York Medical College, Valhalla,  New York,  10595,  United States
North Carolina
      Presbyterian Healthcare, Charlotte,  North Carolina,  28233-3549,  United States
      Raleigh Hematology/Oncology Associates - Wake Practice, Raleigh,  North Carolina,  27609,  United States
Pennsylvania
      Hematology/Oncology Associates of NE Pennsylvania, P.C., Scranton,  Pennsylvania,  18510,  United States
Tennessee
      Associates in Oncology & Hematology, Chattanooga,  Tennessee,  37404,  United States
      Dial Research Associates, Inc., Nashville,  Tennessee,  37205,  United States
Texas
      Presbyterian Hospital of Dallas, Dallas,  Texas,  75231,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0209,  United States
Wisconsin
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States

Study chairs or principal investigators

Alison L. Hannah,  Study Chair,  SUGEN   

Study ID Numbers:  CDR0000067499; SUGEN-SU5416.031; UCLA-9909008
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004252
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08