Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

R115777 Plus Topotecan in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	NYU-9932 NCI-T99-0110, NCT00005990, T99-0110

Objectives

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

Entry Criteria

Disease Characteristics:

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

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

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/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

NYU Cancer Institute at New York University Medical Center

Howard Hochster, MD, Protocol chair		Ph: 212-731-5100 Email: howard.hochster@med.nyu.edu

Registry Information
Official Title		Phase I and Pharmacokinetic Study of the Farnesyl Transferase Inhibitor, R115777, in Combination with Topotecan
Trial Start Date		2000-08-07
Registered in ClinicalTrials.gov		NCT00005990
Date Submitted to PDQ		2000-05-03
Information Last Verified		2006-01-10
NCI Grant/Contract Number		P30-CA16087, U01-CA76642

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