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

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

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

Study Overview

• Status: Completed
• Conditions: Stage IV Colon Cancer; Stage IV Rectal Cancer; Recurrent Colon Cancer; Recurrent Rectal Cancer; Adenocarcinoma of the Rectum; Adenocarcinoma of the Colon
• Intervention / Treatment: Drug: fluorouracil; Drug: eniluracil

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.

• Study Type: Interventional
• Enrollment (Actual): 950
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Eastern Cooperative Oncology Group

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive fluorouracil IV as a continuous infusion for 28 days.	Drug: fluorouracil; Given IV or orally; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil
Experimental: Arm II; Patients receive eniluracil/fluorouracil orally twice a day for 28 days.	Drug: fluorouracil; Given IV or orally; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Drug: eniluracil; Given orally; Other Names: 776C85; ADH300004; ethynyluracil; GW776; GW776C85

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Up to 1 year

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John Hines, Eastern Cooperative Oncology Group

Study record dates

Study Major Dates

• Study Start: April 1, 1999
• Primary Completion (Actual): July 1, 2007

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Recurrence; Adenocarcinoma; Rectal Neoplasms; Colonic 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: NCI-2012-02300; U10CA021115 (U.S. NIH Grant/Contract); E-5296; CDR0000067038 (Registry Identifier: PDQ (Physician Data Query))