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OpenTrials
Completed

NCT Number: NCT00004195

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

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.

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Key information

Conditions

Colorectal Cancer Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Rectal Neoplasms

Age range

19 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion:

  • DISEASE CHARACTERISTICS: Histologically proven or suspicious primary or metastatic colorectal carcinoma undergoing disease resection
  • PATIENT CHARACTERISTICS:A. Age: 19 and over
  • Performance status: Karnofsky 60-100%
  • Not pregnant or nursing Fertile patients must use effective contraception during and for at least 1 month after study
  • PRIOR CONCURRENT THERAPY:
  • Subject has had at least 8 weeks since prior fluorouracil, capecitabine, fluorouracil-uracil, floxuridine, or S-1 Endocrine therapy:
  • No prior or concurrent steroids Radiotherapy:
  • Surgery: No prior emergent surgery (e.g., perforation or obstruction) No prior transplantation
  • At least 8 weeks since any prior drug metabolized by dihydropyrimidine dehydrogenase enzyme At least 8 weeks since prior flucytosine

Exclusion:

  • Severe infection(White Blood Cell Count)WBC>2 times normal
  • Fever
  • Sepsis
  • Subject on immunosuppressives therapy
  • Subjects will serum Bilirubin/Creatinine>2 times normal levels
  • Pregnant /Lactating women
  • Subjects that have received eniluracil or 5-FU(Fluorouracil) within 28 days prior to randomization
  • Subject that have comorbidity illnesses that will increase the likelihood of there death in <5 years

Treatment and study plan

eniluracil

Drug

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

Other names: 5 Fu/eniluracil (eli Lilly), 5-fu/eniluracil, 5fu/eniluraci

conventional colon surgery

Procedure

Only if the subject is amenable to surgical resections

Primary outcomes

  1. 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

Secondary outcomes

  1. 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.

Other outcomes

  1. Specific Aims

    Time frame: Duriation of trial up to 30 days after first dose

    • 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

Sponsors and collaborators

Lead sponsor

University of Alabama at Birmingham

Other

Collaborators

  • Glaxo Wellcome
  • National Cancer Institute (NCI)

Registry information

Official study title

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

Important dates

Study start
1998
Primary completion
1999
Study completion
2001
First posted
Sep 16, 2004
Registry last updated
Jun 15, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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