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

June 12, 2015 updated by: Marty Heslin, University of Alabama at Birmingham

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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 colon surgery
Only if the subject is amenable to surgical resections
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
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 colon surgery
Only if the subject is amenable to surgical resections

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Goal to demonstrate that eniluracil at current clinical doses
Time Frame: 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
Pre-operative and up to 30 days after first dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate DPD recovery and uracil levels
Time Frame: 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.
pre-operative and up to 30 post first dose

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Specific Aims
Time Frame: 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
Duriation of trial up to 30 days after first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alabama at Birmingham

Collaborators

National Cancer Institute (NCI)
Glaxo Wellcome

Investigators

  • Study Chair: Martin J. Heslin, MD, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1998

Primary Completion (ACTUAL)

October 1, 1999

Study Completion (ACTUAL)

May 1, 2001

Study Registration Dates

First Submitted

January 21, 2000

First Submitted That Met QC Criteria

September 15, 2004

First Posted (ESTIMATE)

September 16, 2004

Study Record Updates

Last Update Posted (ESTIMATE)

June 15, 2015

Last Update Submitted That Met QC Criteria

June 12, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067438
  • F980826006 (OTHER: University of Alabama at Birmingham IRB)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe