A Phase II Trial of STA-9090 in Patients With Metastatic Castration-Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Based Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- PFS Proportion Achieved With STA-9090 in Men With CRPC Who Have Received Prior Docetaxel Based Therapy
研究概览
简要总结
Hsp90 inhibitor STA-9090 may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. This phase II trial is studying how well Hsp90 inhibitor STA-9090 works in treating patients with metastatic hormone-resistant prostate cancer previously treated with docetaxel-based chemotherapy
详细描述
PRIMARY OBJECTIVES:
I. To evaluate progression-free survival (PFS) achieved with STA-9090 (Hsp90 inhibitor STA-9090) in men with castration-resistant prostate cancer (CRPC) who have received prior docetaxel based therapy.
SECONDARY OBJECTIVES:
I. To assess the percentage change in prostate-specific antigen (PSA) from baseline to 12 weeks.
II. To assess overall safety and tolerability of STA-9090. III. To evaluate overall survival (OS) outcome in metastatic CRPC who have received prior docetaxel therapy.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed diagnosis of prostate adenocarcinoma with metastasis and objective progression or rising PSA despite androgen deprivation therapy and antiandrogen withdrawal when applicable
- •Progression after docetaxel based chemotherapy is needed as follows:
- •a) If measurable disease present, then either rising PSA, increase in size of the lesion/s or both should be present
- •b) Patients with rising PSA only as progression must demonstrate a rising trend with 2 successive elevations at minimum intervals of 1 week; a minimum PSA of 5 ng/ml, or new areas of bony metastases on bone scan are required for patients with no measurable disease; no minimum PSA requirement for patients with measurable disease
- •Patients should have received at least one prior docetaxel based regimen for metastatic disease; no maximum prior therapy
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- •Life expectancy of at least 3 months
- •Prior radiation therapy or chemotherapy completed at least 28 days prior to enrollment
- •All patients must be documented to be castrate with a testosterone level =< 0.5 ng/ml; luteinizing-hormone-releasing hormone (LHRH) agonist therapy must be continued, if required to maintain castrate levels of testosterone; patients must be off antiandrogens for a minimum of 4 weeks for flutamide and 6 weeks for bicalutamide or nilutamide
- •Absolute neutrophil count >= 1,500 cells/uL
- •Platelets >= 100,000/uL
- •Hemoglobin >= 9.0 g/dL
- •Serum creatinine =< 1.5 x upper limit of normal (ULN); Note: if serum creatinine is > 1.5 x ULN, subject is eligible if the calculated creatinine clearance (CLcr) is >= 50 mL/min
- •Total bilirubin =< 1.5 x ULN
- •For patients without documented bone metastases or for patients with liver metastases: transaminases (aspartate aminotransferase [AST]/serum glutamic oxaloacetic transaminase [SGOT] and/or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase [SGPT]) may be up to 2.5 x institutional ULN if alkaline phosphatase is =< ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are =< ULN
- •For patients with documented bone metastases, the transaminases (AST/SGOT and/or ALT/SGPT) should be less than 2.5 x institutional ULN, without regard to the alkaline phosphatase level
- •Sexually active males must use measures to prevent pregnancy in their partners while on STA-9090
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- •Ability to understand and willingness to sign a written informed consent document
排除标准
- •Major surgery within 4 weeks prior to first dose of STA-9090
- •Poor venous access for study drug administration or would require a peripheral or central indwelling catheter for study drug administration; study drug administration via indwelling catheters is prohibited at this time
- •Use of any chemotherapy or other standard systemic treatments for prostate cancer, including investigational agents within 2 weeks or 6 half- lives of the agent, whichever is shorter, prior to receiving STA-9090; there must be at least 2 weeks between the end of palliative radiation and the start of study drug and all radiation therapy (XRT)-associated toxicities resolved to Grade 1 or 0
- •History of severe allergic or hypersensitivity reactions to excipients (e.g., Polyethylene glycol [PEG] 300 and Polysorbate 80 [i.e. docetaxel])
- •Baseline QTc > 450 msec or previous history of QT prolongation while taking other medications
- •Ventricular ejection fraction (Ef) =< 55% at baseline
- •Any history of current coronary artery disease, myocardial infarction, angina pectoris, angioplasty or coronary bypass surgery
- •History of current uncontrolled dysrhythmias, or requirement for antiarrhythmic medications, or Grade 2 or greater left bundle branch block
- •New York Heart Association class II/III/IV congestive heart failure with a history of dyspnea, orthopnea, or edema that requires current treatment with angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers or diuretics
- •Current or prior radiation therapy to the left hemithorax
- •Treatment with chronic immunosuppressants (e.g. cyclosporine following transplantation)
- •Uncontrolled intercurrent illness including, but not limited to, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: Hsp90 inhibitor STA-9090 (Drug)
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: polymerase chain reaction (Genetic)
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: enzyme-linked immunosorbent assay (Other)
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: RNA analysis (Genetic)
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: spectrophotometry (Other)
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: reverse transcriptase-polymerase chain reaction (Genetic)
Treatment (enzyme inhibitor therapy)
Patients receive Hsp90 inhibitor STA-9090 IV over 1 hour once weekly in weeks 1-3. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: gene expression analysis (Genetic)
结局指标
主要结局
PFS Proportion Achieved With STA-9090 in Men With CRPC Who Have Received Prior Docetaxel Based Therapy
时间窗: At 6 months
Our primary objective was to determine the 6-month PFS rate by using a binary (yes/no) endpoint of 6 months of PFS. Treatment success was defined as achievement of at least 6 months of PFS. Patients who did not complete 6 months of ganetespib therapy for any reason (including death from any cause) were considered treatment failures and were recorded as not achieving the primary endpoint.
次要结局
- Percentage Change in PSA(From baseline to 12 weeks)
- Overall Safety and Tolerability of STA-9090(Day 1, 8, and 15 of each course and at end of treatment)
- OS in Metastatic CRPC Who Have Received Prior Docetaxel Therapy(From first dose to death or the date last known alive)
- Association of PFS With PSA(At 6 months)
- Potential Markers for Predicting Drug Response or Efficacy(At baseline, day 1 of course 3, and end of treatment)
研究者
Elisabeth Heath
Principal Investigator
Barbara Ann Karmanos Cancer Institute