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

University of Alabama at Birmingham28 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Colorectal Cancer

Interventions

eniluracilDRUG

Will be given to either subject pre-operative and metastatic disease

conventional colon surgeryPROCEDURE

Only if the subject is amenable to surgical resections

Eligibility

Sex: ALLMin age: 19 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion: 1. DISEASE CHARACTERISTICS: Histologically proven or suspicious primary or metastatic colorectal carcinoma undergoing disease resection 2. PATIENT CHARACTERISTICS:A. Age: 19 and over 3. Performance status: Karnofsky 60-100% 4. Not pregnant or nursing Fertile patients must use effective contraception during and for at least 1 month after study 5. PRIOR CONCURRENT THERAPY: 6. Subject has had at least 8 weeks since prior fluorouracil, capecitabine, fluorouracil-uracil, floxuridine, or S-1 Endocrine therapy: 7. No prior or concurrent steroids Radiotherapy: 8. Surgery: No prior emergent surgery (e.g., perforation or obstruction) No prior transplantation 9. At least 8 weeks since any prior drug metabolized by dihydropyrimidine dehydrogenase enzyme At least 8 weeks since prior flucytosine Exclusion: 1. Severe infection(White Blood Cell Count)WBC\>2 times normal 2. Fever 3. Sepsis 4. Subject on immunosuppressives therapy 5. Subjects will serum Bilirubin/Creatinine\>2 times normal levels 6. Pregnant /Lactating women 7. Subjects that have received eniluracil or 5-FU(Fluorouracil) within 28 days prior to randomization 8. Subject that have comorbidity illnesses that will increase the likelihood of there death in \<5 years

Outcomes

Primary Outcomes

Primary Goal to demonstrate that eniluracil at current clinical doses

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

Time frame: Pre-operative and up to 30 days after first dose

Secondary Outcomes

Evaluate DPD recovery and uracil levels

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.

Time frame: pre-operative and up to 30 post first dose

Data from ClinicalTrials.gov

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