A Phase I Trial of the Farnesyltransferase Inhibitor, R115777 (NSC# 702818) and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
A Phase I Trial of the Farnesyltransferase Inhibitor, R115777 (NSC# 702818) and Radiotherapy in Patients With Locally Advanced Pancreatic Cancer
RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and may make them more sensitive to radiation therapy. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving tipifarnib together with radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with radiation therapy in treating patients with unresectable locally advanced pancreatic cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, dose-escalation study of tipifarnib.
Patients receive oral tipifarnib once or twice daily on weeks 1-8. Patients also undergo concurrent radiotherapy daily, 5 days a week, on weeks 2-8.
Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed at 1, 3, and 6 months.
PROJECTED ACCRUAL: A total of 8-18 patients will be accrued for this study within 12-15 months.
DISEASE CHARACTERISTICS:
Histologically confirmed pancreatic cancer
Unresectable disease requiring radiotherapy
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No peripheral neuropathy ≥ grade 2
No known allergy to imidazole drugs, including any of the following:
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery