Eniluracil and Surgery in Treating Patients With Primary or Metastatic Colorectal Cancer

Phase 2

Completed

• Conditions: Colorectal Cancer
• Interventions: Drug: eniluracil; Procedure: conventional colon surgery

• Registration Number: NCT00004195
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

RATIONALE: Eniluracil may increase the effectiveness of chemotherapy by blocking tumor enzymes that break down chemotherapy drugs.

PURPOSE: Randomized phase II trial to determine the effectiveness of eniluracil followed by surgery in treating patients who have primary or metastatic colorectal cancer.

Detailed Description

OBJECTIVES: I. Determine the enzymatic activity of dihydropyrimidine dehydrogenase (DPD) in peripheral blood mononuclear cells (PBMC), normal mucosa, or normal liver in patients with primary or metastatic colorectal cancer. II. Evaluate the ability of eniluracil to inactivate DPD in the tumor, PBMCs, and normal tissue in this patient population. III. Assess DPD recovery and uracil levels in PBMCs following surgical resection in these patients.

OUTLINE: This is a randomized, placebo controlled study. Patients are stratified according to colorectal tumor (primary vs metastatic). Patients are randomized into one of two treatment arms. Arm I: Patients receive oral eniluracil twice daily on days -2 and -1 followed by surgical resection and tissue harvest on day 0. Arm II: Patients receive an oral placebo as in arm I followed by surgical resection and tissue harvest on day 0. Patients are followed weekly for 1 month.

PROJECTED ACCRUAL: A total of 20 patients (10 per treatment arm) will be accrued for this study.

Study Timeline

• Study Start: 1998-09
• Primary Completion: 1999-10
• Study First Submitted: 2000-01-21
• Study Completion: 2001-05
• Study First Submitted QC: 2004-09-15
• Study First Posted: 2004-09-16
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-12
• Last Update Posted: 2015-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oral eniluracil 20 mg twice daily	conventional colon surgery	20 mg of eniluracil given twice daily for duration of the study. This subject may have surgery IF tumor is amenable to resection
Placebo	conventional colon surgery	20 mg placebo that will be given for the duration of the study. This subject may have surgery IF tumor is amenable to resection
Oral eniluracil 20 mg twice daily	eniluracil	20 mg of eniluracil given twice daily for duration of the study. This subject may have surgery IF tumor is amenable to resection
Placebo	eniluracil	20 mg placebo that will be given for the duration of the study. This subject may have surgery IF tumor is amenable to resection

Primary Outcome Measures

Name	Time	Method
Primary Goal to demonstrate that eniluracil at current clinical doses	Pre-operative and up to 30 days after first dose	To see if at standard clinical doses are capable of inhibiting DPD in Primary and metastatic colorectal cancer in vivo. Since one of the mechanisms of 5-FU(Fluorouracil) tumor resistance is overexpression of DPD,effective inactivation DPD in tumors by eniluracil in this study will be supportive of the use of eniluracil to overcome this type of 5-FU(Fluorouracil) resistance

Secondary Outcome Measures

Name	Time	Method
Evaluate DPD recovery and uracil levels	pre-operative and up to 30 post first dose	To evaluate the recovery of DPD and uracil levels at 4 more times in the range of postoperative days 5-7,12-16,20-24,and 26-30.