Leucovorin and Fluorouracil With or Without SU5416 in Treating Patients With Metastatic Colorectal Cancer

A Randomized, Open-Label, Multicenter Phase III Study of 5-FU/Leucovorin With or Without Concomitant SU5416 in Patients With Metastatic Colorectal Cancer

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: semaxanib

Detailed Description

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.

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: November 1, 1999
• Primary Completion (Actual): September 1, 2007
• Study Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: January 28, 2000
• First Submitted That Met QC Criteria: April 16, 2004
• First Posted (Estimate): April 19, 2004

Study Record Updates

• Last Update Posted (Estimate): September 11, 2012
• Last Update Submitted That Met QC Criteria: September 10, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: SUGEN-SU5416.031; CDR0000067499; UCLA-9909008