OBJECTIVES:

• Determine the dose-limiting toxic effects of R115777 and topotecan in patients with advanced solid tumors.
• Determine the maximum tolerated dose of this regimen in these patients.
• Determine pharmacokinetic profiles of topotecan alone and in combination with R115777 in these patients.
• Measure the inhibition of ras-farnesylation and topo-1 inhibition in peripheral blood mononuclear cells in these patients when treated with this regimen.
• Determine activity of this treatment in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive oral R115777 twice daily on days 2-21 (in the first course only R115777 begins on day 3) and topotecan IV continuously on days 1-21. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of R115777 and topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced solid tumor not amenable to standard curative therapy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 6 months

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 5 times ULN
• No significant hepatic dysfunction that would preclude study

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• No significant cardiovascular dysfunction that would preclude study

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No malabsorption syndrome, partial or complete bowel obstruction, disease significantly affecting gastrointestinal function, or major resection of the stomach or proximal small bowel
• At least 1 week since prior active infection requiring systemic medical therapy
• No significant organ system dysfunction (neurologic, endocrine) that would preclude study
• No dementia or altered mental status that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No more than 3 prior chemotherapy regimens
• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• No more than 25% of bone marrow volume irradiated
• No prior pelvic radiation
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Not specified