Phase I and Pharmacokinetic Study of the Farnesyl Transferase Inhibitor, R115777, in Combination With Topotecan
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed advanced solid tumor not amenable to standard curative therapy
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Life expectancy:
- •At least 6 months
- •Hematopoietic:
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •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
- •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
- •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
- •Not specified
排除标准
- 未提供