Tipifarnib and Radiation Therapy in Treating Patients With Unresectable Locally Advanced Pancreatic Cancer

OBJECTIVES:

Primary

• Determine the maximum tolerated dose and dose-limiting toxic effects of tipifarnib when administered with radiotherapy in patients with unresectable locally advanced pancreatic cancer.

Secondary

• Determine the 3-month clinical response in patients treated with this regimen.

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

• Locally advanced disease
• Unresectable disease requiring radiotherapy

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• AST or ALT < grade 2 elevation
• Bilirubin ≤ 2.0 mg/dL* NOTE: *Prior biliary stent procedure to normalize bilirubin levels allowed

Renal

• Creatinine ≤ 1.5 times normal

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:

• Clotrimazole
• Ketoconazole
• Miconazole
• Econazole
• Fenticonazole
• Isoconazole
• Sulconazole
• Tioconazole
• Terconazole

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior experimental or standard chemotherapy and recovered
• No concurrent experimental chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior upper abdominal radiotherapy

Surgery

• Not specified