Identifying Mechanisms of Resistance to Enzalutamide (MDV3100) Treatment in Men With Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 3
- 主要终点
- PSA response, a binary variable indicating whether the PSA level has declined >= 50% within 12 weeks of beginning enzalutamide treatment
研究概览
简要总结
This research trial studies molecular features and pathways in predicting drug resistance in patients with castration-resistant prostate cancer that has spread to other parts of the body and who are receiving enzalutamide. Studying samples of blood and tissue in the laboratory from patients receiving enzalutamide may help doctors learn more about molecular features and pathways that may cause prostate cancer to be resistant to the drug.
详细描述
PRIMARY OBJECTIVES:
I. To assess the correlations between baseline molecular features and pathways and prostate-specific antigen (PSA) response (</>= 50% decline) at 12 weeks versus (vs.) baseline.
SECONDARY OBJECTIVES:
I. To assess the correlations between the baseline molecular features and pathways and progression-free survival (defined as time from day 1 of study drug treatment to date of radiographic progression or clinical progression), disease-specific survival (defined as the time from day 1 of study drug to date of death from prostate cancer), and overall survival (defined as time from day 1 of study drug treatment to date of death from any cause).
II. To assess the correlations between the baseline molecular features and pathways and time to PSA progression.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- •Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
- •Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
- •Willingness to undergo a tumor biopsy at baseline and at disease progression
- •Serum testosterone level < 50 ng/dL at screening
- •Progressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria:
- •PSA progression defined by a minimum of three rising PSA levels with an interval of >= 1 week between each determination; the PSA value at screening should be >= 2 ug/L (2 ng/ml)
- •Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- •Bone disease progression defined by two or more new lesions on bone scan
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Clinically able, in the opinion of the investigator, to receive MDV3100 (enzalutamide)
- •Willing and able to give informed consent
- •A minimum of 4 weeks elapsed off of anti-androgen therapy prior to enrollment for flutamide and 6 weeks for bicalutamide and nilutamide without evidence of an anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most recent anti-androgen therapy or in whom the response to the most recent anti-androgen was for < 3 months require only a 2 week washout period prior to first dose of study drug
排除标准
- •Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
- •Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed)
- •Platelet count < 75,000/uL
- •Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time PTT > 1.5 times the institutional upper limit of normal (ULN)
- •Structurally unstable bone lesions suggesting impending fracture
- •Previous treatment with MDV3100, ARN-509, or BMS-641988
- •Medical contraindications to stopping aspirin, Coumadin or other anticoagulants for 1 week prior to image-guided tumor biopsies
- •Plans to initiate treatment with an investigational agent while on study prior to discontinuation of MDV3100 treatment
- •A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm
研究组 & 干预措施
Ancillary-Correlative (genetic analysis)
Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.
干预措施: Cytology Specimen Collection Procedure (Other)
Ancillary-Correlative (genetic analysis)
Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.
干预措施: Enzalutamide (Drug)
Ancillary-Correlative (genetic analysis)
Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide and after the time of disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
PSA response, a binary variable indicating whether the PSA level has declined >= 50% within 12 weeks of beginning enzalutamide treatment
时间窗: Within 12 weeks
Will be reported with 95% exact confidence interval.
次要结局
- Maximal PSA decline observed while on study(Up to 4 years)
- Molecular features(Up to 4 years)
- Degree of PSA decline(12 weeks)
- Disease-specific survival(Time from day 1 of the study drug to date of death from prostate cancer, assessed up to 4 years)
- Overall survival(Time from day 1 of study drug treatment to date of death from any cause, assessed up to 4 years)
- Time to PSA progression(Up to 4 years)
- Objective response(Up to 4 years)
- Progression for a subgroup of patients who have metastatic castration resistant prostate cancer and have received enzalutamide treatment(Up to 4 years)
- Progression-free survival(Time from day 1 of study drug treatment to date of first documented radiographic progression or clinical progression, assessed up to 4 years)
研究者
Tom Beer
Principal Investigator
OHSU Knight Cancer Institute