Phase I Study of 17- Allylamino-17 Demethoxygeldanamycin (17-AAG) in Combination With Paclitaxel in Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Phase 2 recommended doses of tanespimycin
研究概览
简要总结
This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given together with paclitaxel in treating patients with metastatic or unresectable solid tumor. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin and paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining 17-N-allylamino-17-demethoxygeldanamycin with paclitaxel may kill more tumor cells
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with paclitaxel in patients with metastatic or unresectable solid malignancy.
II. Determine the dose-limiting and non-dose-limiting toxic effects of this regimen in these patients.
III. Determine the pharmacokinetics of this regimen in these patients. IV. Determine tumor response in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Histologically confirmed solid malignancy
- •Metastatic or unresectable disease
- •Not amenable to standard curative or palliative therapy
- •No known brain metastases
- •Performance status - ECOG 0-2
- •More than 12 weeks
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •WBC ≥ 3,000/mm^3
- •AST and ALT ≤ 2.5 times upper limit of normal
- •Bilirubin normal
- •Creatinine normal
- •Creatinine clearance ≥ 60 mL/min
- •QTc < 450 msec for male patients (470 msec for female patients)
- •LVEF > 40% by MUGA
- •No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
- •No myocardial infarction within the past year
- •No New York Heart Association class III or IV congestive heart failure
- •No poorly controlled angina
- •No history of uncontrolled dysrhythmia or requirement for antiarrhythmic drugs
- •No history of congenital long QT syndrome
- •No active ischemic heart disease within the past year
- •No left bundle branch block
- •No other significant cardiac disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double barrier contraception for at least 1 week before, during, and for at least 2 weeks after study participation
- •No prior allergy to eggs
- •No prior allergic reaction to compounds of similar chemical or biologic composition to 17-AAG or paclitaxel
- •No peripheral neuropathy > grade 1
- •No concurrent uncontrolled illness
- •No active or ongoing infection
- •No psychiatric illness or social situation that would preclude study compliance
- •No concurrent granulocyte colony-stimulating factors
- •Prior paclitaxel allowed
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
- •No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)
- •More than 4 weeks since prior radiotherapy
- •No prior radiotherapy that included the heart in the field (e.g., mantle radiotherapy)
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent therapeutic-dose warfarin for anticoagulation
- •No concurrent medications that may prolong QTc interval
- •No other concurrent investigational agents
- •No other concurrent anticancer agents or therapies
排除标准
- 未提供
研究组 & 干预措施
Treatment (tanespimycin, paclitaxel)
Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: tanespimycin (Drug)
Treatment (tanespimycin, paclitaxel)
Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel (Drug)
Treatment (tanespimycin, paclitaxel)
Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (tanespimycin, paclitaxel)
Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Phase 2 recommended doses of tanespimycin
时间窗: 28 days
Tabulated according to the NCI CTC.
次要结局
未报告次要终点