SWOG-S9635 Fluorouracil Plus Ethynyluracil in Treating Patients With Advanced Colorectal Cancer That Has Not Responded to Fluorouracil

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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: ethynyluracil
  • 10mg/m2/dose, PO, Days 1-28, q 5wk
• Drug: fluorouracil
  • 1.0mg/m2/dose, PO, Days 1-28 BID, q 5wk

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 776C85 + 5-FU
  • 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.

• DISEASE CHARACTERISTICS: 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
• PATIENT CHARACTERISTICS: Age: Over 18 Performance status: SWOG 0-2 Life expectancy: Not specified 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
• PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Chemotherapy: See
• Disease Characteristics 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: See
• Disease Characteristics 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Southwest Oncology Group Other

Overall Clinical Trial Officials and Contacts

Cynthia G. Leichman, MD Study Chair Albany Medical College  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00003254

Study ID Number: CDR0000066138

ClinicalTrials.gov Identifier: NCT00003254

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database