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

NCT ID: NCT00004195

Last Updated: 2015-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-09-30
• Study Completion Date: 2001-05-31

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

eniluracil

Intervention Type: DRUG

Will be given to either subject pre-operative and metastatic disease

conventional colon surgery

Intervention Type: PROCEDURE

Only if the subject is amenable to surgical resections

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

Group Type: PLACEBO_COMPARATOR

eniluracil

Intervention Type: DRUG

Will be given to either subject pre-operative and metastatic disease

conventional colon surgery

Intervention Type: PROCEDURE

Only if the subject is amenable to surgical resections

Interventions

eniluracil

Will be given to either subject pre-operative and metastatic disease

Intervention Type: DRUG

conventional colon surgery

Only if the subject is amenable to surgical resections

Intervention Type: PROCEDURE

Other Intervention Names

5 Fu/eniluracil (eli Lilly); 5-fu/eniluracil; 5fu/eniluraci

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Glaxo Wellcome

INDUSTRY

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Marty Heslin

Chief of Surgical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martin J. Heslin, MD

Role: STUDY_CHAIR

University of Alabama at Birmingham

Other Identifiers

F980826006

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000067438

Identifier Type: -

Identifier Source: org_study_id