Phase I and Clinical Pharamcologic Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Combination With Probenecid in Adults With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 2
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. Probenecid may increase the effectiveness of 10-propargyl-10-deazaaminopterin by making tumor cells more sensitive to the drug.
PURPOSE: Phase I trial to study the effectiveness of combining 10-propargyl-10-deazaaminopterin and probenecid in treating patients who have advanced solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of 10-propargyl-10-deazaaminopterin and probenecid in patients with advanced solid tumors.
- Determine the therapeutic activity of this regimen in these patients.
- Determine the toxic effects of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a dose-escalation study of 10-propargyl-10-deazaaminopterin (PDX) and probenecid.
Patients receive probenecid IV and PDX IV on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive sequentially escalating doses of probenecid and PDX until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 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 cancer that is potentially incurable by standard chemotherapy, radiotherapy, or surgical procedures
- •Failed prior first-line therapy (patients are also eligible if no effective first-line therapy exists)
- •Previously treated or clinically stable brain metastases are allowed
- •No leukemia or lymphoma
- •No clinically significant pleural effusions or ascites
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 70-100%
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •WBC at least 4,000/mm^3
- •Platelet count at least 160,000/mm^3
- •Hemoglobin greater than 10 g/dL
- •Serum and RBC folate normal
- •Bilirubin no greater than 1.5 mg/dL
- •SGOT or SGPT less than 2 times upper limit of normal
- •Creatinine no greater than 1.2 mg/dL OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular:
- •No unstable angina
- •No congestive heart failure
- •No cardiac arrhythmia
- •Homocysteine normal
- •No grade III or IV edema
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for 6 months after study
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •See Disease Characteristics
- •At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas or mitomycin) and recovered
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •See Disease Characteristics
- •At least 3 weeks since prior radiotherapy to bone marrow-containing areas and recovered
- •See Disease Characteristics
- •No prior pneumonectomy
- •No concurrent folic acid or potentially nephrotoxic agents
排除标准
- 未提供