A Randomized, Double-Blind, Phase II, Efficacy and Safety Study of MDV3100 Versus Bicalutamide in Castrate Men With Metastatic Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- enzalutamide
- Conditions
- Prostatic Neoplasms
- Sponsor
- Astellas Pharma Inc
- Enrollment
- 375
- Locations
- 88
- Primary Endpoint
- Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: enzalutamide
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.
Intervention: bicalutamide
Outcomes
Primary Outcomes
Progression Free Survival (PFS) Based on Independent Central Review (ICR) Assessment
Time Frame: 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.
Secondary Outcomes
- 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).)