Evaluation of Dihydropyrimidine Dehydrogenase (DPD) Activity in Surgically Resected Primary and Metastatic Colorectal Cancer After 48 hr Pretreatment With Eniluracil
19 Years
80 Years
Both
Colorectal Cancer
Trial Information
Evaluation of Dihydropyrimidine Dehydrogenase (DPD) Activity in Surgically Resected Primary and Metastatic Colorectal Cancer After 48 hr Pretreatment With Eniluracil
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.
Inclusion 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 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Primary Goal to demonstrate that eniluracil at current clinical doses
Outcome Description:
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
Outcome Time Frame:
Pre-operative and up to 30 days after first dose
Safety Issue:
Yes
Principal Investigator
Martin J. Heslin, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Alabama at Birmingham
Authority:
United States: Federal Government
Study ID:
CDR0000067438
NCT ID:
NCT00004195
Start Date:
September 1998
Completion Date:
May 2001
Related Keywords:
- Colorectal Cancer
- 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
- Colorectal Neoplasms
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