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

January 21, 2000
March 14, 2013
September 1998
October 1999   (final data collection date for primary outcome measure)
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
Not Provided
Complete list of historical versions of study NCT00004195 on ClinicalTrials.gov Archive Site
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.
Not Provided
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
Not Provided
 
Eniluracil and Surgery in Treating Patients With Primary or Metastatic Colorectal Cancer
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Colorectal Cancer
  • 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
  • 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
    Interventions:
    • Drug: eniluracil
    • Procedure: conventional surgery
  • 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
    Interventions:
    • Drug: eniluracil
    • Procedure: conventional surgery
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
May 2001
October 1999   (final data collection date for primary outcome measure)

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
Both
19 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00004195
CDR0000067438, F980826006
Yes
Marty Heslin, University of Alabama at Birmingham
University of Alabama at Birmingham
  • National Cancer Institute (NCI)
  • Glaxo Wellcome
Study Chair: Martin J. Heslin, MD University of Alabama at Birmingham
University of Alabama at Birmingham
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP