Phase I Study of the Hsp90 Inhibitor, PU-H71, in Patients With Refractory Solid Tumors and Low-Grade Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)
研究概览
简要总结
Background:
- PU-H71 is an experimental drug used to treat cancer. It works by blocking a protein in tumors. When this protein is blocked, it affects other proteins inside the cell that cancers need to grow. Researchers want to study whether PU-H71 is a safe and effective way to treat solid tumors and non-Hodgkin's lymphoma.
Objectives:
- To evaluate the safety and effectiveness of PU-H71 in solid tumors and non-Hodgkin's lymphoma that have not responded to standard treatments.
Eligibility:
- Individuals at least 18 years of age who have solid tumors or non-Hodgkin's lymphoma that have not responded to standard treatments.
Design:
- Patients will be screened with a physical exam, medical history, blood tests, and imaging studies.
- Patients will receive PU-H71 as a 1-hour dose on days 1 and 8 of a 21-day cycle of treatment. The first treatment cycle will be done in the hospital so that patients can be monitored. The next treatment cycles will be done on an outpatient basis.
- Patients will have blood and urine tests and eye exams.
- Patients will provide tumor samples for study.
- Patients will have imaging studies to monitor tumor response to treatment.
- Patients will continue to take PU-H71 for as long as side effects remain tolerable and their tumor or lymphoma does not worsen. Study researchers may adjust the dose if needed.
详细描述
Background:
-PU-H71 is a synthetic HSP90 inhibitor which can bind both open and closed conformations of HSP90. It demonstrates extended tumor retention and client protein degradation, while being rapidly cleared from normal tissues. It has shown complete tumor responses and retained sensitivity to retreatment in vivo.
Primary Objectives:
- To establish the safety and tolerability of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and lowgrade non-Hodgkin's lymphoma (NHL).
- To establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and low-grade NHL.
- To determine the pharmacokinetics of PU-H71 administered on a once weekly, 2 weeks out of 3 schedule, in patients with refractory solid tumors and low-grade NHL.
Secondary Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
PU-H71
PU-H71 will be administered intravenous (IV) over one hour, once weekly, 2 weeks out of 3, (i.e., on days 1 and 8) every 21 days
干预措施: PU-H71 (Drug)
结局指标
主要结局
Number of Participants With Cycle 1 Dose-limiting Toxicities (DLTs)
时间窗: Cycle 1 (21 days)
A DLT was defined as an adverse event that occurred during cycle 1, was thought to be related to study drug administration, and met one of the following criteria: grade ≥ 3 non-hematologic toxicities (except diarrhea, nausea, vomiting without maximal supportive therapy; alopecia), grade 4 hematologic toxicities (except lymphopenia), and grade 2 ocular toxicity that did not resolve to ≤ grade 1 within 2 weeks. Occurrence of a DLT resulted in a dose reduction following resolution to grade ≤ 2. No more than 2 dose reductions were allowed per patient on study.
Number of Participants With Adverse Events Possibly, Probably, or Definitely Related to Study Drug
时间窗: 3 years and two months and 11 days
Severity of adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 1 Mild adverse event (AE), Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, and Grade 5 Death related to AE.
Maximum Tolerated Dose (MTD) of PU-H71
时间窗: Cycle 1 (21 days)
The MTD is the dose level at which no more than 1 of 6 patients experience DLT during the first cycle of treatment, and the dose below that at which at least 2 (of ≤ 6) patients have DLT as a result of the drug.
次要结局
- Urinary Excretion (%)(Every void post-treatment on day 1 of cycle 1)
- Clearance(Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.)
- Number of Participants According to Best Response Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1)(Baseline and every 6 weeks up to 18 weeks)
- Number of Days on Treatment(up to 126 days)
- Maximum Observed Plasma Concentration (Cmax)(Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.)
- Terminal Half-life (T1/2)(Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.)
- Area Under the Concentration-Time Curve From Time 0 to 24 Hours [AUC(0-24)](Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.)
- Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0-∞)](Before the start of infusion, 30 minutes after the start of infusion, 5 minutes before completion of infusion, and at 1.5, 2, 3, 4, 7, 10, and 24 hours after the start of infusion on day 1 during cycle 1.)
研究者
Alice Chen, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)