SWOG-S9635 Fluorouracil Plus Ethynyluracil in Advanced Colorectal Cancer Not Responded to Fluorouracil

A Phase II Trial of 5-Fluorouracil Plus 776C85 in Patients With Advanced Resistant Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Ethynyluracil may help fluorouracil kill more cancer cells by making tumor cells more sensitive to the drug.

PURPOSE: Phase II trial to study the effectiveness of fluorouracil plus ethynyluracil in treating patients with advanced colorectal cancer that has not responded to fluorouracil.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: ethynyluracil; Drug: fluorouracil

Detailed Description

OBJECTIVES: I. Assess the confirmed response rate to fluorouracil (5-FU) plus ethynyluracil (776C85) in patients with metastatic colorectal cancer that has been demonstrated to be resistant to 5-FU. II. Assess time to progression and survival in this group of patients. III. Assess the frequency and severity of toxicities associated with this treatment.

OUTLINE: Patients are stratified according to relapse while receiving adjuvant therapy (relapse within 12 months of completing adjuvant therapy vs relapse while receiving adjuvant therapy). Patients receive oral doses of ethynyluracil (776C85) and fluorouracil twice daily for 28 days followed by 1 week of rest. Treatment continues every 5 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months the first year, every 4 months the second year, and every 6 months thereafter.

PROJECTED ACCRUAL: A total of 35-75 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • MBCCOP - University of South Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Greater Phoenix
    • Phoenix, Arizona, United States, 85012
      • Veterans Affairs Medical Center - Phoenix (Hayden)
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock (McClellan)
  • California
    • Long Beach, California, United States, 90822
      • Veterans Affairs Medical Center - Long Beach
    • Los Angeles, California, United States, 90033-0800
      • USC/Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 91010
      • Beckman Research Institute, City of Hope
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Francisco, California, United States, 94115-0128
      • UCSF Cancer Center and Cancer Research Institute
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
    • Travis Air Force Base, California, United States, 94535
      • David Grant Medical Center
  • Colorado
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
    • Denver, Colorado, United States, 80262
      • University of Colorado Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
    • Fort Gordon, Georgia, United States, 30905-5650
      • Dwight David Eisenhower Army Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96859-5000
      • Tripler Army Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Illinois
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40511-1093
      • Veterans Affairs Medical Center - Lexington
    • Lexington, Kentucky, United States, 40536-0084
      • Albert B. Chandler Medical Center, University of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Veterans Affairs Medical Center - New Orleans
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University Health Sciences Center - Shreveport
    • Shreveport, Louisiana, United States, 71130
      • Veterans Affairs Medical Center - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Jamaica Plain, Massachusetts, United States, 02130
      • Veterans Affairs Medical Center - Boston (Jamaica Plain)
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0752
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48105
      • Veterans Affairs Medical Center - Ann Arbor
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids Clinical Oncology Program
    • Southfield, Michigan, United States, 48075-9975
      • Providence Hospital - Southfield
  • Mississippi
    • Biloxi, Mississippi, United States, 39531-2410
      • Veterans Affairs Medical Center - Biloxi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
    • Keesler AFB, Mississippi, United States, 39534-2576
      • Keesler Medical Center - Keesler AFB
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Veterans Affairs Medical Center - Kansas City
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63110-0250
      • St. Louis University Health Sciences Center
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Springfield, Missouri, United States, 65807
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
    • Albuquerque, New Mexico, United States, 87131
      • MBCCOP - University of New Mexico HSC
  • New York
    • Brooklyn, New York, United States, 11209
      • Veterans Affairs Medical Center - Brooklyn
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Barrett Cancer Center, The University Hospital
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Kettering, Ohio, United States, 45429
      • CCOP - Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
    • Oklahoma City, Oklahoma, United States, 73104
      • Veterans Affairs Medical Center - Oklahoma City
  • Oregon
    • Portland, Oregon, United States, 97201-3098
      • Oregon Cancer Center at Oregon Health Sciences University
    • Portland, Oregon, United States, 97207
      • Veterans Affairs Medical Center - Portland
    • Portland, Oregon, United States, 97213
      • CCOP - Columbia River Program
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Texas
    • Dallas, Texas, United States, 75235-9154
      • Simmons Cancer Center - Dallas
    • Fort Sam Houston, Texas, United States, 78234
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-1329
      • University of Texas Medical Branch
    • Lubbock, Texas, United States, 79423
      • Texas Tech University Health Science Center
    • San Antonio, Texas, United States, 78284-7811
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78284
      • Veterans Affairs Medical Center - San Antonio (Murphy)
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Huntsman Cancer Institute
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest

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

• Histologically or cytologically proven metastatic colorectal cancer
• Prior surgery required
• No prior treatment for metastatic disease
• Disease progression while on fluorouracil adjuvant therapy
• Bidimensionally measurable disease
• Age: Over 18
• Performance status: SWOG 0-2
• Hematopoietic: Platelet count at least 100,000/mm3, Absolute granulocyte count at least 1,500/mm3
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT no greater than 3 times ULN (no greater than 5 times ULN if liver involvement)
• Renal: Creatinine clearance at least 50 mL/min
• Other: Must be able to swallow and retain oral medications No nutritional support by gastrostomy feeding tube or parenteral support No intractable vomiting or nausea
• Patients with history of prior malignancy must be currently disease free and off all therapy for that malignancy
• Not pregnant or nursing Fertile patients must use effective contraception
• Biologic therapy: No concurrent immunotherapy Chemotherapy; At least 3 weeks since prior chemotherapy and recovered; No concurrent flucytosine; No other concurrent chemotherapy
• Endocrine therapy: No concurrent hormonal therapy
• Radiotherapy: Prior adjuvant pelvic radiation or radiation to one area of recurrence allowed At least 4 weeks since prior radiotherapy and recovered Total area of bone marrow irradiation must not exceed 25% No concurrent radiotherapy
• Surgery: At least 2 weeks since prior surgery for colorectal cancer and recovered No prior resection of the stomach or small intestine
• Other: No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 776C85 + 5-FU; 776C85, 10mg/m2/dose, PO, Days 1-28 (BID), q 5 wk; 5-FU, 1.0mg/m2/dose, PO, Days 1-28 (BID), q 5 wk.	Drug: ethynyluracil; 10mg/m2/dose, PO, Days 1-28, q 5wk; Other Names: 776C85; Drug: fluorouracil; 1.0mg/m2/dose, PO, Days 1-28 BID, q 5wk; Other Names: 5-FU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Response Rate	To assess the confirmed response rate to 5-fluorouracil plus 776C85 in patients with measurable, disseminated colorectal cancer that has been demonstrated to be resistant to 5-fluorouracil.	Once every 10 weeks until off treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression and Survival	To assess time to progression and survival in this group of patients.	Once every 10 weeks until progression
Toxicities	To assess the frequency and severity of toxicities associated with this treatment.	Once each week during treatment

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Cynthia G. Leichman, MD, Albany Medical College

Publications and helpful links

General Publications

• Leichman CG, Chansky K, Macdonald JS, Doukas MA, Budd GT, Giguere JK, Abbruzzese JL; Southwest Oncology Group. Biochemical modulation of 5-fluorouacil through dihydropyrimidine dehydrogenase inhibition: a Southwest Oncology Group phase II trial of eniluracil and 5-fluorouracil in advanced resistant colorectal cancer. Invest New Drugs. 2002 Nov;20(4):419-24. doi: 10.1023/a:1020662113061.

Study record dates

Study Major Dates

• Study Start: April 1, 1998
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): October 1, 2003

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: June 15, 2004
• First Posted (Estimate): June 16, 2004

Study Record Updates

• Last Update Posted (Estimate): March 8, 2012
• Last Update Submitted That Met QC Criteria: March 6, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; 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; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil; Eniluracil
• Other Study ID Numbers: CDR0000066138; U10CA032102 (U.S. NIH Grant/Contract); S9635 (Other Identifier: SWOG)