Phase 2 Trial of TAK-700 (Also Known as Orteronel) Without Prednisone for Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- PSA Response, Defined as Occurrence of PSA Decline to Greater Than or Equal to 50% From Baseline
研究概览
简要总结
This phase II trial studies how well orteronel works in treating patients with metastatic hormone-resistant prostate cancer. Orteronel may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To assess the relationship between circulating tumor cell (CTC)-based androgen receptor (AR) expression level and >=-50% prostate-specific antigen (PSA) decline following 12 weeks of therapy with TAK-700 (orteronel).
SECONDARY OBJECTIVES:
I. To assess changes in PSA and CTC levels and time to PSA progression (best response, decline at 12 weeks as continuous variable, etc.) with or without prior docetaxel-based treatment.
II. To assess measurable disease response and time to radiographic disease progression for castration-resistant prostate cancer (CRPC) with or without prior docetaxel-based treatment.
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
- •Histologically confirmed adenocarcinoma of the prostate
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
- •Patients, even if surgically sterilized (i.e., status post vasectomy), who agree to practice effective barrier contraception during the entire study treatment period and for 4 months after the last dose of study drug, or
- •Agree to completely abstain from intercourse
- •Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be =< 2.5 x the upper limit of normal (ULN)
- •Total bilirubin =< 1.5 x ULN
- •Estimated creatinine clearance using the Cockcroft-Gault formula must be > 40 mL/minute
- •Absolute neutrophil count (ANC) >= 1500 cells/microliter
- •Platelet count >= 100,000 cells/microliter
- •Testosterone < 50 ng/dL
- •Screening calculated ejection fraction of >= 50% by multiple gated acquisition (MUGA) scan or echocardiogram; metastatic progression on primary androgen-deprivation therapy (medical or surgical castration)
- •Progression requiring a change in oncologic therapy defined by any of the following:
- •Radiographic progression: appearance or increase in measurable lesions on cross-sectional imaging or appearance of one or more new lesions on bone scan * Rising PSA (>= 2 ng/ml) which has risen on two occasions >= 1 week apart
- •Clinical progression evidenced by increased pain or other cancer-related symptoms
- •Patients should have recovered from prior oncologic therapies to a Common Terminology Criteria (CTC) grade =< 1 except stable neuropathy or alopecia at National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade =< 2; if rapid clinical progression is documented by imaging, changes in PSA, or symptoms, then study treatment can begin >= 2 weeks from prior therapy; otherwise, the following time periods between prior anti-cancer therapies and study treatment day 1 will apply:
- •>= 3 weeks for prior cytotoxic therapies
- •>= 4 weeks for flutamide or nilutamide
- •>= 6 weeks for bicalutamide
- •>= 6 weeks since bone targeted radiopharmaceutical (e.g. samarium-153, radium-223)
- •Gonadotropin-releasing hormone (GnRH) agonists (leuprolide acetate, goserelin, etc.) or antagonists (degarelix, etc.) should be continued in patients without surgically-induced castrate androgen levels
- •For chemotherapy naïve castration-resistant prostate cancer who are moderately symptomatic or who have hepatic metastasis: subjects must not be a candidate for docetaxel-based chemotherapy.
排除标准
- •History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of grade > 2 (NCI CTCAE, version 4), thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g. pericardial effusion, restrictive cardiomyopathy) within 6 months prior to first dose of study drug; chronic stable atrial fibrillation on stable anticoagulant therapy is allowed
- •New York Heart Association class III or IV heart failure
- •Electrocardiogram (ECG) abnormalities of:
- •Q-wave infarction, unless identified 6 or more months prior to screening
- •Corrected QT (QTc) interval > 460 msec
- •Patient has received other investigational drugs within 28 days before enrollment
- •Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy
- •Known hypersensitivity to compounds related to TAK-700 or to TAK-700 excipients
- •Uncontrolled hypertension despite appropriate medical therapy (blood pressure [BP] of greater than 160 mmHg systolic and 90 mmHg diastolic at 2 separate measurements no more than 60 minutes apart during the screening visit); Note: patients may be rescreened after adjustment of antihypertensive medications
- •Known active chronic hepatitis B or C, life-threatening illness unrelated to cancer, or any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with participation in this study
- •Likely inability to comply with the protocol or cooperate fully with the investigator and site personnel
- •Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption or tolerance of TAK-700, including difficulty swallowing tablets
- •Prior treatment with >= 3 lines of cytotoxic chemotherapy for metastatic prostate cancer
- •Prior treatment with TAK-700
研究组 & 干预措施
Treatment (orteronel)
Patients receive orteronel 300 mg PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: orteronel (Drug)
Treatment (orteronel)
Patients receive orteronel 300 mg PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
PSA Response, Defined as Occurrence of PSA Decline to Greater Than or Equal to 50% From Baseline
时间窗: At 12 weeks
Standard descriptive methods will be used to summarize PSA. Values will be tabulated as outlined in the Prostate Cancer Working Group 2 (PCWG2) criteria and presented as Kaplan-Meier survival curves, as appropriate.
Androgen Receptor (AR) Protein Expression Levels in CTCs
时间窗: Up to 4 weeks
The two-sample t-test will be used. Once association between AR protein expression levels and response is established, graphical methods such as receiver-operator curves (ROC) or more quantitative methods such as the maximal chi-square method to determine whether there might be a cut-point with either great sensitivity or great specificity (or both) for identifying a cohort with either a high or low likelihood of prostate-specific antigen (PSA) response.
次要结局
- Best PSA Response(Up to 24 weeks)
- Duration of Response Using RECIST Version 1.1 and PCWG2 Criteria(Up to 3 years)
- Overall Response Rate Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and PCWG2 Criteria(Up to 3 years)
- Number of Participants With Grade 3 or Higher Toxicity(30 days)
- Absolute Change in PSA(Baseline to 24 weeks)