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

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.

• Drug: eniluracil
  Will be given to either subject pre-operative and metastatic disease
  Other Names:

  • 5 Fu/eniluracil (eli Lilly)
  • 5-fu/eniluracil
  • 5fu/eniluraci
• Procedure: conventional surgery
  Only if the subject is amenable to surgical resections

• Active Comparator: Oral eniluracil 20 mg twice daily
  20 mg of eniluracil given twice daily for duration of the study. This subject may have surgery IF tumor is amenable to resection
  Interventions:

  • Drug: eniluracil
  • Procedure: conventional surgery
• Placebo Comparator: Placebo
  20 mg placebo that will be given for the duration of the study. This subject may have surgery IF tumor is amenable to resection
  Interventions:

  • Drug: eniluracil
  • Procedure: conventional surgery

Inclusion:

1. DISEASE CHARACTERISTICS: Histologically proven or suspicious primary or metastatic colorectal carcinoma undergoing disease resection
2. PATIENT CHARACTERISTICS:A. Age: 19 and over B.Performance status: Karnofsky 60-100% C.Not pregnant or nursing Fertile patients must use effective contraception during and for at least 1 month after study
3. PRIOR CONCURRENT THERAPY:

A.Subject has had at least 8 weeks since prior fluorouracil, capecitabine, fluorouracil-uracil, floxuridine, or S-1 Endocrine therapy:

B. No prior or concurrent steroids Radiotherapy:

C. Surgery: No prior emergent surgery (e.g., perforation or obstruction) No prior transplantation D. 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

• National Cancer Institute (NCI)
• Glaxo Wellcome