Phase I and Pharmacokinetic Study of the Farnesyl Transferase Inhibitor, R115777, in Combination With Topotecan
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
Phase I and Pharmacokinetic Study of the Farnesyl Transferase Inhibitor, R115777, in Combination With Topotecan
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Howard S. Hochster, MD
Investigator Role:
Study Chair
Investigator Affiliation:
New York University School of Medicine
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000067979
NCT ID:
NCT00005990
Start Date:
August 2000
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
