R115777 Plus Topotecan in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of R115777 plus topotecan in treating patients who have advanced solid tumors.

Detailed Description
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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.

Official Title
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Phase I and Pharmacokinetic Study of the Farnesyl Transferase Inhibitor, R115777, in Combination With Topotecan

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: tipifarnib
* Drug: topotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tipifarnib|nan|
|Drug: topotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific