Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003873
First received: November 1, 1999
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

Randomized phase III trial to compare the effectiveness of fluorouracil given by infusion with that of fluorouracil plus eniluracil given by mouth in treating patients who have metastatic, recurrent, or residual advanced colorectal cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if fluorouracil is more effective with or without eniluracil for advanced colorectal cancer


Condition Intervention Phase
Adenocarcinoma of the Colon
Adenocarcinoma of the Rectum
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: fluorouracil
Drug: eniluracil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Trial Comparing a 28 Day Schedule of Daily Oral 5-FU Plus Eniluracil to Protracted Intravenous Infusion in Previously Untreated Patients With Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Enrollment: 950
Study Start Date: April 1999
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive fluorouracil IV as a continuous infusion for 28 days.
Drug: fluorouracil
Given IV or orally
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Experimental: Arm II
Patients receive eniluracil/fluorouracil orally twice a day for 28 days.
Drug: fluorouracil
Given IV or orally
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: eniluracil
Given orally
Other Names:
  • 776C85
  • ADH300004
  • ethynyluracil
  • GW776
  • GW776C85

Detailed Description:

OBJECTIVES:

I. Compare the response rate, response duration, and survival of patients with advanced colorectal cancer treated with oral fluorouracil (5-FU) and eniluracil or with protracted infusion 5-FU.

II. Compare the toxicity of these treatment regimens in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to performance status (0 vs 1-2) and measurable disease (yes vs no). Patients are randomized to one of two treatment arms.

ARM I: Patients receive fluorouracil IV as a continuous infusion for 28 days.

ARM II: Patients receive eniluracil/fluorouracil orally twice a day for 28 days.

Treatment continues every 35 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at least every 10 weeks for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with measurable or nonmeasurable histologically confirmed adenocarcinoma of the colon and rectum are eligible provided patient has metastatic, recurrent or residual disease, and tumor is beyond hope of surgical eradication; all pre-study scans documenting disease must be done =< 4 weeks prior to randomization

    • Measurable tumor is defined as a known mass that can be clearly measured in two dimensions by physical examination, CT scan, radionuclide liver scan, or on chest x-ray by a ruler or calipers; the largest diameter of the lesion must measure >= 2 cm by at least one method of evaluation
  • Patients must have had no prior therapy for advanced disease
  • Patients may have had prior adjuvant treatment with 5-FU provided that the last dose was received > 12 months prior to entering the study; no prior chemotherapy other than adjuvant 5-FU is allowed
  • Patients with prior radiotherapy are acceptable, but patients should have measurable or nonmeasurable disease outside the radiation port and/or progressive disease within the previously radiated volume; in addition, it must be at least 2 weeks since administration of radiation therapy and all signs of toxicity must have abated
  • Bilirubin =< 1.5 x upper limit of normal (ULN)
  • SGOT =< 3 x ULN
  • Because Eniluracil changes the metabolism of 5-FU such that it is excreted primarily by the kidneys, an estimated creatinine clearance calculated using the Cockcroft and Gault formula must be obtained in patients with a serum creatinine > institutional normal limits; the estimated creatinine clearance must be >= 50 ml/min prior to starting treatment with Eniluracil/5-FU; if not, a measured creatinine clearance must be done (using a 24 hour urine collection); the measured creatinine clearance must be > 50 ml/min for the patient to be eligible
  • Absolute neutrophil count >= 2000 mm³
  • Platelet count >= 100,000 mm³
  • ECOG performance status 0-2
  • No evidence of significant active infection (e.g., pneumonia, peritonitis, wound abscess, etc.) at time of study entry
  • No evidence of serious intercurrent illness such as uncontrolled diabetes mellitus, hypothyroidism, malabsorption syndrome or heart failure
  • No prior neoplastic diseases (within 5 years) aside from the current malignancy or curatively resected melanoma, skin cancer or cervical carcinoma in situ
  • No treatment with folinic acid, interferon, flucytosine or topical 5-FU within the previous 14 days
  • Not pregnant or lactating; pregnant and lactating women are excluded from the study because effects on the fetus are unknown and there may be a risk of increased fetal wastage
  • Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003873

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: John Hines Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003873     History of Changes
Other Study ID Numbers: NCI-2012-02300, E-5296, U10CA021115, CDR0000067038
Study First Received: November 1, 1999
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Colonic Neoplasms
Colorectal Neoplasms
Rectal Neoplasms
Carcinoma
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
5-ethynyluracil
Fluorouracil
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014