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

SWOG Cancer Research Network

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: fluorouracil

Drug: ethynyluracil

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00003254

S9635 (Other Identifier)

CDR0000066138

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

75 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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