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

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
fluorouracil
leucovorin calcium
semaxanib
Sponsored by
Pfizer
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Alabama Oncology, LLC
  • Office of Richard Shapiro, Benjamin Stafford, and Sharon J. Yee
  • Scripps Clinic
  • Tower Hematology Oncology Medical Group
  • Jonsson Comprehensive Cancer Center, UCLA
  • St. Francis Hospital
  • Comprehensive Cancer Care Specialists of Boca Raton
  • H. Lee Moffitt Cancer Center and Research Institute
  • Queen's Medical Center
  • Mary Bird Perkins Cancer Center
  • Johns Hopkins Oncology Center
  • Cancer Center of Boston
  • Michigan State University
  • University of Minnesota Cancer Center
  • APN-IMPATH Research Corporation
  • Hackensack University Medical Center
  • New York Medical College
  • Presbyterian Healthcare
  • Raleigh Hematology/Oncology Associates - Wake Practice
  • Hematology/Oncology Associates of NE Pennsylvania, P.C.
  • Associates in Oncology & Hematology
  • Dial Research Associates, Inc.
  • Presbyterian Hospital of Dallas
  • University of Texas Medical Branch
  • University of Texas - MD Anderson Cancer Center
  • University of Wisconsin Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
January 28, 2000
Last Updated
September 10, 2012
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00004252
Brief Title
Leucovorin and Fluorouracil With or Without SU5416 in Treating Patients With Metastatic Colorectal Cancer
Official Title
A Randomized, Open-Label, Multicenter Phase III Study of 5-FU/Leucovorin With or Without Concomitant SU5416 in Patients With Metastatic Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
November 1999 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
September 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Intervention Type
Drug
Intervention Name(s)
semaxanib

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alison L. Hannah, MBBS
Organizational Affiliation
SUGEN
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Oncology, LLC
City
Montgomery
State/Province
Alabama
ZIP/Postal Code
36106-2801
Country
United States
Facility Name
Office of Richard Shapiro, Benjamin Stafford, and Sharon J. Yee
City
Arcadia
State/Province
California
ZIP/Postal Code
91007-7678
Country
United States
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Tower Hematology Oncology Medical Group
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
St. Francis Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
Comprehensive Cancer Care Specialists of Boca Raton
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33428
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Queen's Medical Center
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96813
Country
United States
Facility Name
Mary Bird Perkins Cancer Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
Johns Hopkins Oncology Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Cancer Center of Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02120
Country
United States
Facility Name
Michigan State University
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48824
Country
United States
Facility Name
University of Minnesota Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
APN-IMPATH Research Corporation
City
Fort Lee
State/Province
New Jersey
ZIP/Postal Code
07024
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Presbyterian Healthcare
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28233-3549
Country
United States
Facility Name
Raleigh Hematology/Oncology Associates - Wake Practice
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27609
Country
United States
Facility Name
Hematology/Oncology Associates of NE Pennsylvania, P.C.
City
Scranton
State/Province
Pennsylvania
ZIP/Postal Code
18510
Country
United States
Facility Name
Associates in Oncology & Hematology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Dial Research Associates, Inc.
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37205
Country
United States
Facility Name
Presbyterian Hospital of Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555-0209
Country
United States
Facility Name
University of Texas - MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
University of Wisconsin Comprehensive Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

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

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