SWOG-S9635 Fluorouracil Plus Ethynyluracil in Advanced Colorectal Cancer Not Responded to Fluorouracil

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Ethynyluracil may help fluorouracil kill more cancer cells by making tumor cells more sensitive to the drug. PURPOSE: Phase II trial to study the effectiveness of fluorouracil plus ethynyluracil in treating patients with advanced colorectal cancer that has not responded to fluorouracil.

Detailed Description
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OBJECTIVES: I. Assess the confirmed response rate to fluorouracil (5-FU) plus ethynyluracil (776C85) in patients with metastatic colorectal cancer that has been demonstrated to be resistant to 5-FU. II. Assess time to progression and survival in this group of patients. III. Assess the frequency and severity of toxicities associated with this treatment. OUTLINE: Patients are stratified according to relapse while receiving adjuvant therapy (relapse within 12 months of completing adjuvant therapy vs relapse while receiving adjuvant therapy). Patients receive oral doses of ethynyluracil (776C85) and fluorouracil twice daily for 28 days followed by 1 week of rest. Treatment continues every 5 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months the first year, every 4 months the second year, and every 6 months thereafter. PROJECTED ACCRUAL: A total of 35-75 patients will be accrued for this study.

Official Title
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A Phase II Trial of 5-Fluorouracil Plus 776C85 in Patients With Advanced Resistant Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: ethynyluracil
* Drug: fluorouracil


Participation Criteria
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Eligibility Criteria
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Histologically or cytologically proven metastatic colorectal cancer Prior surgery required No prior treatment for metastatic disease Disease progression while on fluorouracil adjuvant therapy Bidimensionally measurable disease Age: Over 18 Performance status: SWOG 0-2 Hematopoietic: Platelet count at least 100,000/mm3, Absolute granulocyte count at least 1,500/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT or SGPT no greater than 3 times ULN (no greater than 5 times ULN if liver involvement) Renal: Creatinine clearance at least 50 mL/min Other: Must be able to swallow and retain oral medications No nutritional support by gastrostomy feeding tube or parenteral support No intractable vomiting or nausea Patients with history of prior malignancy must be currently disease free and off all therapy for that malignancy Not pregnant or nursing Fertile patients must use effective contraception Biologic therapy: No concurrent immunotherapy Chemotherapy; At least 3 weeks since prior chemotherapy and recovered; No concurrent flucytosine; No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy Radiotherapy: Prior adjuvant pelvic radiation or radiation to one area of recurrence allowed At least 4 weeks since prior radiotherapy and recovered Total area of bone marrow irradiation must not exceed 25% No concurrent radiotherapy Surgery: At least 2 weeks since prior surgery for colorectal cancer and recovered No prior resection of the stomach or small intestine Other: No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 776C85 + 5-FU<br>776C85, 10mg/m2/dose, PO, Days 1-28 (BID), q 5 wk; 5-FU, 1.0mg/m2/dose, PO, Days 1-28 (BID), q 5 wk. | Drug: ethynyluracil<br>* 10mg/m2/dose, PO, Days 1-28, q 5wk<br>* Other names: 776C85;Drug: fluorouracil<br>* 1.0mg/m2/dose, PO, Days 1-28 BID, q 5wk<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Response Rate | To assess the confirmed response rate to 5-fluorouracil plus 776C85 in patients with measurable, disseminated colorectal cancer that has been demonstrated to be resistant to 5-fluorouracil. | Once every 10 weeks until off treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression and Survival | To assess time to progression and survival in this group of patients. | Once every 10 weeks until progression | 
| Toxicities | To assess the frequency and severity of toxicities associated with this treatment. | Once each week during treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer