A Phase 2 Open-Label Study to Investigate the Pharmacodynamics and Clinical Activity of IPI-504 in Patients With Castration-Resistant Prostate Cancer Stratified by Prior Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 10
- 主要终点
- Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate
研究概览
简要总结
To determine:
- Anti-tumor activity of IPI-504 in 2 groups of subjects with hormone resistant prostate cancer.
- Group A - subjects who have not previously received chemotherapy
- Group B - sujects who have received prior chemotherapy or could not tolerate chemotherapy.
- Clinical response will be determined by PSA and radiological response
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. Inhibition of HSP-90 leads to the proteasomal degradation of these proteins.
In patients with HRPC,there are several proteins that are important in the progression of HRPC, including AR, AKT and Her-2. All of these are client proteins of Hsp90 and in response to Hsp90 inhibition are degraded by their proteasome. Preclinical studies have shown that Hsp90 inhibition causes a dose dependent degradation of these client proteins and growth inhibition of prostate cancer in xenograft tumors.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Adenocarcinoma of the prostate
- •Resolution of acute toxic side effects of prior chemotherapy
- •Castration resistant disease despite ongoing chemical or surgical castration
- •PSA greater than or equal to 2
- •Group A -
- •No Prior treatment for prostate cancer with cytotoxic chemotherapy (neoadjuvant, adjuvant treatment permitted if more than 2 years out)
- •Radiographic evidence of metastatic disease
- •Prior tx with docetaxel-minimum of 2 cycles with progression by RECIST or PSA or intolerant of tx
- •Maximum of 3 prior chemotherapies
排除标准
- •Small cell carcinoma of the prostate
- •Treatment within 2 weeks with approved, investigational, or small molecule
- •Treatment within 4 weeks with biologic or external beam radiation
- •ANC <1,500 cells m3; Platelets <100,000 mm3; Hemoglobin <9.0g/dL
- •AST/ALT >2.5 ULN
- •Serum creatinine >3.0mg/dL
- •Active keratitis or keratoconjunctivitis
- •Previous treatment with 17-AAG, DMAG; or any other HSP-90 inhibitor
- •Baseline Qtc >450 mses
研究组 & 干预措施
IPI-504: Group A
No Prior treatment for prostate cancer with cytotoxic chemotherapy (adjuvant or neoadjuvant chemotherapy is acceptable if completed >2 years prior to study)
干预措施: IPI-504 (Drug)
IPI-504: Group B
- Must have evidence of radiographic metastatic disease
- Must have been treated with a docetaxel-based chemotherapy regimen for HRPC with a minimum of 2 cycles with either PSA or RECIST defined radiographic progression during or witin 60 days of completeing docetaxel based chemotheraph or be intolerant of docetaxel-based chemotherapy
- No more than three prior chemotherapies regimens for HRPC
干预措施: IPI-504 (Drug)
结局指标
主要结局
Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate
时间窗: 12 Weeks
次要结局
- Assess the safety and tolerability of IPI-504 in patients with hormone resistant prostate cancer(12 Weeks)