Phase I Dose Escalation Study of Tirapazamine (NSC 130181) in Combination With Carboplatin and Paclitaxel in Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 8
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 combining tirapazamine, carboplatin, and paclitaxel in treating patients who have advanced malignant solid tumors.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of tirapazamine in combination with carboplatin and paclitaxel in patients with advanced solid tumors who have or have not received prior chemotherapy.
- Assess the toxicity and preliminary efficacy of this regimen in these patients.
- Determine the pharmacokinetic profile of this regimen in these patients.
- Investigate potential predictors of response by studying patient tissue specimens after receiving this regimen.
OUTLINE: This is a dose-escalation study of tirapazamine. Patients are stratified according to prior chemotherapy status (previously untreated vs previously treated).
Patients receive tirapazamine IV over 2 hours, paclitaxel IV over 3 hours, and carboplatin IV over 30 minutes. Treatment continues every 21 days for a maximum of 8 courses in the absence of unacceptable toxicity or disease progression. Some patients may continue therapy in the absence of unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tirapazamine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 12 patients in the previously untreated stratum are treated at the MTD.
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 or cytologically confirmed advanced or metastatic malignant solid tumor not curable by resection or other standard therapy
- •No symptomatic brain metastases
- •Brain metastases allowed provided controlled with surgical excision and/or radiotherapy
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Karnofsky 60-100%
- •Life expectancy:
- •At least 3 months
- •Hematopoietic:
- •WBC at least 3,000/mm3
- •Absolute neutrophil count at least 1,000/mm3
- •Platelet count at least 100,000/mm3
- •Bilirubin no greater than 1.5 mg/dL
- •SGOT no greater than 2 times upper limit of normal
- •Creatinine normal
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular:
- •No New York Heart Association class III or IV congestive heart failure
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after study
- •No history of allergic reactions to appropriate diuretics or antiemetics administered in conjunction with protocol chemotherapy (e.g., 5-HT3 antagonists)
- •No other concurrent uncontrolled illness that would preclude study therapy
- •No medical, social, or psychological factors that would preclude study therapy
- •No clinically significant hearing loss
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •At least 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) and recovered
- •No more than 2 prior chemotherapy regimens
- •No prior combination paclitaxel and carboplatin
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- •See Disease Characteristics
- •At least 4 weeks since prior radiotherapy and recovered
- •No concurrent radiotherapy
- •See Disease Characteristics
- •Recovered from prior surgery
- •At least 30 days since other prior investigational drugs
- •No other concurrent anticancer therapy
- •No other concurrent investigational agents
排除标准
- 未提供