Eniluracil and Surgery in Treating Patients With Primary or Metastatic Colorectal Cancer
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ClinicalTrials.gov Identifier: NCT00004195 |
Recruitment Status
:
Completed
First Posted
: September 16, 2004
Last Update Posted
: June 15, 2015
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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 or disease | Intervention/treatment | Phase |
---|---|---|
Colorectal Cancer | Drug: eniluracil Procedure: conventional colon surgery | Phase 2 |
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 (Clinical Trial) |
Actual Enrollment : | 28 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Care Provider, 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 |
Study Start Date : | September 1998 |
Actual Primary Completion Date : | October 1999 |
Actual Study Completion Date : | May 2001 |

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
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Drug: eniluracil
Will be given to either subject pre-operative and metastatic disease
Other Names:
Procedure: conventional colon surgery
Only if the subject is amenable to surgical resections
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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
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Drug: eniluracil
Will be given to either subject pre-operative and metastatic disease
Other Names:
Procedure: conventional colon surgery
Only if the subject is amenable to surgical resections
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- 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
- 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.
- 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

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Ages Eligible for Study: | 19 Years to 80 Years (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004195
Study Chair: | Martin J. Heslin, MD | University of Alabama at Birmingham |
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 ( Other Identifier: University of Alabama at Birmingham IRB ) |
First Posted: | September 16, 2004 Key Record Dates |
Last Update Posted: | June 15, 2015 |
Last Verified: | June 2015 |
Keywords provided by Marty Heslin, 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 Eniluracil Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |