Colorectal Cancer
Conditions
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
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.
Interventions
DRUGeniluracil
Will be given to either subject pre-operative and metastatic disease
PROCEDUREconventional colon surgery
Only if the subject is amenable to surgical resections
Sponsors
National Cancer Institute (NCI)
Glaxo Wellcome
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Specific Aims | Duriation of trial up to 30 days after first dose | 1. Determine the enzymatic activity of DPD in PBMC's normal mucosa or normal liver and in primary and secondary colorectal cancers 2. Confirm the ability of eniluracil to inactivate DPD in tumors as well as PBMC's and normal tissue 3. Assess DPD recovery and uracil levels in PBMC's at 5-7,12-16,20-24,and 26-30 days postoperatively |
Outcome results
None listed