A Phase I Trial of 5-Fluorouracil Given With 776C85 (GW776) and Low-Dose Leucovorin in Adult Patients With Solid Tumors

Launched by NATIONAL CANCER INSTITUTE (NCI) · Dec 9, 2002

Keywords

ClinConnect Summary

The primary purpose of this Phase I protocol is to develop an orally administered regimen of fluorouracil (5-FU) given with fixed doses of leucovorin (LV) and 776C85 (GW776), a mechanism-based inhibitor of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme involved in the catabolism of 5-FU. In the presence of 776C85, 5-FU is cleared by renal mechanisms. The schedule employed is intended to mimic the pharmacologic profile associated with a 24 hour weekly continuous infusion of 5-FU without the need for an indwelling central venous catheter. The target population is adult cancer...

Gender

ALL

Eligibility criteria

• DISEASE CHARACTERISTICS:
• • Histologically proven solid tumor that has failed standard therapy or for which no such therapy exists.
• • Tumor may be locally advanced and unresectable, recurrent and/or metastatic.
• • Lymphomas with minimal or no involvement of bone marrow are also eligible.
• • No primary malignancies or metastatic disease of the CNS.
• • No symptomatic pre-existing peripheral neuropathy.
• PRIOR/CURRENT THERAPY:
• BIOLOGIC THERAPY:
• • No immunotherapy within past 4 weeks.
• • Recovered from toxic effects.
• CHEMOTHERAPY:
• • No chemotherapy within past 4 weeks (6 weeks for nitrosoureas).
• • No mitomycin within past 12 weeks.
• • Recovered from toxic effects.
• • ENDOCRINE THERAPY: Not specified.
• RADIOTHERAPY:
• • No radiotherapy within past 2 weeks (8 weeks for strontium therapy).
• • Recovered from toxic effects.
• • SURGERY: Recovered from prior surgery.
• • OTHER: No concurrent cimetidine.
• PATIENT CHARACTERISTICS:
• • AGE: 18 and over.
• • PERFORMANCE STATUS: ECOG 0-2.
• • LIFE EXPECTANCY: Not specified.
• HEMATOPOIETIC:
• • Absolute granulocyte count at least 2000/mm(3);
• • Platelet count at least 100,000/mm(3).
• HEPATIC:
• • Bilirubin no greater than 2 times upper normal limit;
• • SGOT/SGPT no greater than 4 times upper normal limit.
• RENAL:
• • Creatinine no greater than 1.6 mg/dL;
• • Creatinine clearance greater than 55 mL/min.
• OTHER:
• • Not pregnant or nursing.
• • Fertile patients must use effective contraception.
• • Not HIV positive.
• • No active infections requiring intravenous antibiotic therapy.
• • No other serious concurrent illness.
• • No evidence of hemolytic uremic syndrome.