Clinical trial NCT00004195: Eniluracil and Surgery in Treating Patients With Primary or Metastatic Colorectal Cancer
Official title: Evaluation of Dihydropyrimidine Dehydrogenase (DPD) Activity in Surgically Resected Primary and Metastatic Colorectal Cancer After 48 hr Pretreatment With Eniluracil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: stage I colon cancer
stage II colon cancer
stage III colon cancer
stage IV colon cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Glaxo Wellcome
First posted: 2004-09-16
Enrollment: 28
Sex: ALL
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary Goal to demonstrate that eniluracil at current clinical doses
timeFrame: Pre-operative and up to 30 days after first dose
Secondary outcomes:
measure: Evaluate DPD recovery and uracil levels
timeFrame: pre-operative and up to 30 post first dose
Other outcomes:
measure: Specific Aims
timeFrame: Duriation of trial up to 30 days after first dose
Locations:
Study officials:
affiliation: University of Alabama at Birmingham
name: Martin J. Heslin, MD
role: STUDY_CHAIR
References: