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

This study has been completed.
Sponsor:
Collaborators:
Glaxo Wellcome
Information provided by (Responsible Party):
Marty Heslin, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00004195
First received: January 21, 2000
Last updated: March 14, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Drug: eniluracil
Procedure: conventional surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Dihydropyrimidine Dehydrogenase (DPD) Activity in Surgically Resected Primary and Metastatic Colorectal Cancer After 48 hr Pretreatment With Eniluracil

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Primary Goal to demonstrate that eniluracil at current clinical doses [ Time Frame: Pre-operative and up to 30 days after first dose ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Evaluate DPD recovery and uracil levels [ Time Frame: pre-operative and up to 30 post first dose ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Specific Aims [ Time Frame: Duriation of trial up to 30 days after first dose ] [ Designated as safety issue: Yes ]
    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


Enrollment: 28
Study Start Date: September 1998
Study Completion Date: May 2001
Primary Completion Date: October 1999 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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 surgery
Only if the subject is amenable to surgical resections

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.

  Eligibility

Ages Eligible for Study:   19 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004195

Sponsors and Collaborators
University of Alabama at Birmingham
Glaxo Wellcome
Investigators
Study Chair: Martin J. Heslin, MD University of Alabama at Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: Marty Heslin, Chief of Surgical Oncology, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00004195     History of Changes
Other Study ID Numbers: CDR0000067438, F980826006
Study First Received: January 21, 2000
Last Updated: March 14, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Alabama at Birmingham:
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

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
5-ethynyluracil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014