R115777 Plus Topotecan in Treating Patients With Advanced Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: topotecan hydrochloride; Drug: tipifarnib

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: August 1, 2000
• Primary Completion (Actual): September 1, 2006

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): November 9, 2012
• Last Update Submitted That Met QC Criteria: November 8, 2012
• Last Verified: January 1, 2006

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Tipifarnib; Topotecan
• Other Study ID Numbers: CDR0000067979; NYU-9932; NCI-T99-0110