A Phase I Dose Escalation Study of the PKC Inhibitor, Aurothiomalate (ATM) in Patients With Advanced Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 17
- 试验地点
- 3
- 主要终点
- Biologic activity
研究概览
简要总结
RATIONALE: Gold sodium thiomalate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of gold sodium thiomalate in treating patients with advanced non-small cell lung cancer.
详细描述
OBJECTIVES:
- To determine the maximum tolerated dose of gold sodium thiomalate in patients with advanced non-small cell lung cancer.
- To describe the toxicities associated with this treatment.
- To describe any preliminary evidence of biologic activity.
- To further assess the correlation between PKCι expression and the antitumor effects of gold sodium thiomalate.
- To study the association of clinical (toxicity and/or tumor response or activity) with pharmacokinetic/pharmacodynamic parameters.
- To describe anti-proliferative activity of gold sodium thiomalate through 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging.
OUTLINE: This is a dose-escalation study of gold sodium thiomalate.
Patients receive gold sodium thiomalate intramuscularly on days 1, 8, 15 and 22. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive gold sodium thiomalate once every 4 weeks until a total cumulative dose of 1 gram is delivered.
Blood samples are collected at baseline and prior to therapy in weeks 3, 5, 7, 9, and 11. Samples are analyzed by mass spectometry for pharmacokinetics. Paraffin-embedded tumor tissue samples are analyzed for PKC_l expression and antitumor activity. Antiproliferative effects of gold sodium thiomalate are analyzed by 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed advanced non-small cell lung cancer
- •No known standard therapy for disease that is potentially curative or definitely capable of extending life expectancy
- •No symptomatic or worsening CNS metastases despite optimal therapy
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-2
- •Life expectancy ≥ 12 weeks
- •ANC ≥ 1,500/µL
- •Platelet count ≥ 100,000/µL
- •Total bilirubin ≤ 2 times upper limit of normal (ULN)
- •AST ≤ 3 times ULN (5 times ULN if liver involvement)
- •Creatinine ≤ 1.2 times ULN
- •Hemoglobin ≥ 9.0 g/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Must be willing to provide blood and tissue samples
- •No uncontrolled infection
- •No New York Heart Association class III or IV heart disease
- •No known allergy to gold sodium thiomalate
- •PRIOR CONCURRENT THERAPY:
- •Recovered from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
- •No prior chemotherapy within the past 3 weeks
- •No prior mitomycin C or nitrosoureas within the past 6 weeks
- •No prior immunotherapy within the past 3 weeks
- •No prior biologic therapy within the past 3 weeks
- •No prior radiotherapy within the past 3 weeks
- •No prior radiotherapy to > 25% of bone marrow
- •No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation)
- •No concurrent prophylactic colony stimulating factors
排除标准
- 未提供
结局指标
主要结局
Biologic activity
Maximum tolerated dose
Toxicity
Correlate PKCl expression with antitumor effects of gold sodium thiomalate
Correlate toxicity and/or tumor response or activity with pharmacokinetic and pharmacodynamic parameters
Anti-proliferative activity of gold sodium thiomalate by PET scan
次要结局
未报告次要终点