A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 375
- 试验地点
- 88
- 主要终点
- Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment
研究概览
简要总结
The purpose of this study was to determine the efficacy and safety of oral enzalutamide compared to bicalutamide in castrate men with metastatic prostate cancer who have progressed while on Luteinizing Hormone Receptor Hormone (LHRH) agonist/antagonist or after receiving a bilateral orchiectomy.
详细描述
An open-label period was added to the main protocol. Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over bicalutamide as assessed by the primary endpoint, all ongoing enzalutamide treated participants and ongoing or previous bicalutamide treated participants that met entry criteria were offered open-label enzalutamide at the discretion of the participant and study investigators.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 without neuroendocrine differentiation or small cell features
- •Ongoing androgen deprivation therapy with a Luteinizing Hormone Receptor Hormone (LHRH) agonist or antagonist at a stable dose and schedule within 4 weeks of randomization or bilateral orchiectomy (i.e., surgical or medical castration)
- •Metastatic disease documented by one of the following:
- •At least two bone lesions on bone scan, or
- •Soft tissue disease documented by computed tomography (CT)/ magnetic resonance imaging (MRI), or
- •Unequivocal pelvic adenopathy short axis > 2.0 cm in diameter by CT/MRI
- •Progressive disease at study entry defined as one or more of the following three criteria occurring in the setting of castrate levels of testosterone:
- •Prostate Specific Antigen (PSA) progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value should be ≥ 2 µg/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
- •Asymptomatic or mildly symptomatic from prostate cancer (i.e. the score on the Brief Pain Inventory-Short Form (BPI-SF) Question #3 must be < 4); no use of opiate analgesics for prostate cancer-related pain currently or anytime within 4 weeks prior to randomization
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, including subjects with decreased performance status not attributed to progressive and symptomatic prostate cancer
- •Estimated life expectancy of ≥ 12 months
- •Able to swallow the study drug and comply with study requirements
- •A male subject and his female spouse/partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom as a barrier method of contraception) starting at Screening and continuing throughout the study period, and for 3 months after final study drug administration. Two acceptable forms of birth control include:
- •Condom (barrier method of contraception), AND
- •In addition to a condom, one of the following acceptable forms of contraception is required:
- •Established use of oral, injected or implanted hormonal methods of contraception.
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS).
- •Barrier methods of contraception: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- •Tubal ligation for at least 6 months prior to Screening
- •Vasectomy or other surgical castration at least 6 months prior to Screening
排除标准
- •Prior cytotoxic chemotherapy for prostate cancer
- •Severe concurrent disease, infection, or comorbidity that would make the subject inappropriate for enrollment
- •Known or suspected brain and/or skull metastasis or active epidural disease
- •History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer
- •Current or prior treatment with estrogens and/or drugs with anti-androgenic properties such as spironolactone > 50 mg/day, or progestational agents for the treatment of prostate cancer within 6 months prior to randomization
- •Current or prior use of ketoconazole for the treatment of prostate cancer
- •Use of antiandrogens within 6 weeks prior to randomization
- •Documented prior disease progression while receiving antiandrogens. Disease progression defined as PSA progression, radiographic progression and/or clinical deterioration.
- •Current or prior treatment with 5-α reductase inhibitors or anabolic steroids within 6 months prior to randomization
- •Prior use of systemic glucocorticoids (the equivalent of 10 mg of prednisone) within 3 months prior to randomization or expectation of their use during the study
- •Radiation therapy to bone lesions or prostatic bed within 4 weeks prior to randomization
- •Major surgery within 2 months prior to randomization
- •History of seizure including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness or transient ischemic attack within 12 months prior to randomization
- •Clinically significant cardiovascular disease including myocardial infarction within past six months or uncontrolled angina within past three months
研究组 & 干预措施
Enzalutamide
Participants received enzalutamide 160 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
干预措施: enzalutamide (Drug)
Bicalutamide
Participants received bicalutamide 50 mg orally once daily until confirmed radiographic disease progression, skeletal-related event or the initiation of a new antineoplastic therapy.
干预措施: bicalutamide (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment
时间窗: From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.
PFS is the time from randomization to the date of the first progression event detected. A progression event was defined as objective evidence of radiographic disease progression based on the assessments by the ICR, skeletal-related event, initiation of new antineoplastic therapy or death by any cause, whichever occurred first. Radiographic disease progression was defined as either a progression in soft tissue on computed tomography (CT)/magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and/or a progression in bone lesions on bone scan (≥ 2 new bone lesions) confirmed by the next bone scan. A skeletal-related event was any radiation therapy or surgery to bone, pathologic bone fracture, spinal cord compression or change in antineoplastic therapy to treat bone pain. The initiation of new antineoplastic therapy included any new therapy for the treatment of disease progression after the study drug administration started.
次要结局
- PFS Based on Investigator Assessment(From randomization until the data cut-off date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Prostate-specific Antigen (PSA) Response by Week 13(Baseline to Week 13)
- Best PSA Response(Baseline to the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Time to PSA Progression(From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Time to PSA ≤ 4 ng/mL(From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Time to ≥ 30% PSA Decline From Baseline(From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Time to ≥ 50% PSA Decline From Baseline(From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Time to ≥ 90% PSA Decline From Baseline(From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Radiographic PFS Based on ICR Assessment(From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Percentage of Participants With an Objective Response(From randomization until the data cutoff date of 19 October 2014, median duration of treatment was 11.6 months in the enzalutamide arm and 5.8 months in the bicalutamide arm.)
- Percentage of Participants With Adverse Events(From initiation of study drug up to 30 days after last dose of study drug or the 30-day safety follow-up visit, whichever was last (Median duration of treatment was 11.6 months in enzalutamide arm and 5.8 in bicalutamide arm, 12.6 in the total arm).)