A Phase 1, Safety Assessment and Pharmacokinetic Study of IPI-504 in Patients With Either Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) or Advanced or Metastatic Soft Tissue Sarcomas (STS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 4
- 主要终点
- To recommend a dose for subsequent studies of IPI-504
研究概览
简要总结
The primary objectives of the study are:
- Determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
- Recommend a dose for subsequent studies of IPI-504
详细描述
IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's role in the cell is to control the proper folding, function, and viability of various "client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. In patients with GIST, mutations in the tyrosine kinase receptor Kit play a critical role in the pathogenesis of this disease. Inhibition of Kit signaling with the tyrosine kinase inhibitor Imatinib (IM) is a very effective treatment for GIST patients. However, new mutations arise in Kit conferring resistance to IM treatment which results in disease progression. Kit is a client protein of Hsp90 and is sensitive to IPI-504. In Soft Tissue Sarcomas, there may be genetic abnormalities that lead to the expression of certain proteins that drive the growth of cancer. These cancer-driving proteins may be stimulated by HSP90. This provides a scientific rationale for Phase 1 clinical testing of IPI-504 in patients with advanced GIST and STS who have failed prior therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Pathologically confirmed diagnosis of GIST or STS
- •Failed prior therapies
- •ECOG performance status of 0-2
- •Ability to adhere to the study visit schedule and all protocol requirements
排除标准
- •Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor
- •Participation in any investigational drug study or treatment with any other kinase inhibitor therapy within 2 weeks preceding start of treatment
- •Concurrent radiation therapy is not permitted
- •Concurrent treatment with any agent that alters CYP3A activity
- •Concurrent treatment with any agent that may prolong the QTc interval
- •Myocardial infarction or active ischemic heart disease within 6 months
- •History of arrhythmia
- •Baseline QTc >450
- •Grade 3 or greater peripheral neuropathy
- •Renal insufficiency, serum creatinine >1.5 x ULN
- •Platelets < 100,000 mm3
- •AST and / or ALT > 2.5 x ULN
- •ANC <1,500 cells/mm3
- •Alkaline phosphatase > 2.5 x ULN
- •Amylase and lipase > 1.5 x ULN
- •Hemoglobin < 9.0 g/dL
研究组 & 干预措施
1
Schedule A: Doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration.
干预措施: IPI-504 (Drug)
2
Schedule B: Doses occur on Days 1, 4, 8, 11, 15, and 18 (twice weekly for 3 weeks continuously).
干预措施: IPI-504 (Drug)
结局指标
主要结局
To recommend a dose for subsequent studies of IPI-504
时间窗: 18 months
To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
时间窗: 18 months
次要结局
- To examine the pharmacokinetic (PK) parameters of IPI-504 in GIST and STS patients(18 months)
- To assess in a preliminary way the potential anti-tumor activity of IPI-504 in GIST and STS.(18 months)
- To explore potential pharmacodynamic (PD) markers of biologic activity of IPI-504 in GIST and STS.(18 months)