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

Colorectal Cancer Clinical Trial

Official title:

Evaluation of Dihydropyrimidine Dehydrogenase (DPD) Activity in Surgically Resected Primary and Metastatic Colorectal Cancer After 48 hr Pretreatment With Eniluracil

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004195
• Other study ID #: CDR0000067438
• Secondary ID: F980826006
• Status: Completed
• Phase: Phase 2
• First received: January 21, 2000
• Last updated: June 12, 2015
• Start date: September 1998
• Est. completion date: May 2001

Study information

• Verified date: June 2015
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: May 2001
• Est. primary completion date: October 1999
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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

Procedure:
• conventional colon surgery
Only if the subject is amenable to surgical resections

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Glaxo Wellcome, National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Specific Aims	Determine the enzymatic activity of DPD in PBMC's normal mucosa or normal liver and in primary and secondary colorectal cancers; Confirm the ability of eniluracil to inactivate DPD in tumors as well as PBMC's and normal tissue; Assess DPD recovery and uracil levels in PBMC's at 5-7,12-16,20-24,and 26-30 days postoperatively	Duriation of trial up to 30 days after first dose	Yes
Primary	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	Pre-operative and up to 30 days after first dose	Yes
Secondary	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.	pre-operative and up to 30 post first dose	Yes