A Phase 2 Study Determining Safety and Tolerability of Enzalutamide (Formerly MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients
Overview
- Phase
- Phase 2
- Intervention
- enzalutamide
- Conditions
- Metastatic Castration-Resistant Prostate Cancer
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Number of Participants With Adverse Events (AEs)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study was to explore the safety and tolerability of enzalutamide in combination with abiraterone acetate plus prednisone. Subjects diagnosed with cancer of the prostate that was getting worse and spreading to the bone despite receiving hormone treatment were enrolled and received study treatment until disease progression.
Detailed Description
For the study duration, all subjects maintained androgen deprivation with a gonadotropin releasing hormone (GnRH) agonist or antagonist or orchiectomy. Study drug was administered until disease progression. Disease progression was defined as a composite endpoint consisting of either clinical deterioration, radiographic progression or prostate-specific antigen (PSA) progression according to the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
- •Presence of metastatic disease to the bone
- •Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration)
- •Subject receiving bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to Day 1
- •Progressive disease defined as one or more of the following three criteria (Note: subjects who received an antiandrogen must demonstrate disease progression following discontinuation of antiandrogen):
- •PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥ 2 ng/mL
- •Soft tissue disease progression as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
- •Bone disease progression defined by PCWG2 criteria (two or more new lesions on bone scan compared with prior scan)
- •Subject previously treated with chemotherapy must have no more than two prior chemotherapy regimens for the treatment of metastatic prostate cancer
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Exclusion Criteria
- •Known or suspected metastases in the brain
- •Absolute neutrophil count \< 1,000/μL, platelet count \< 75,000/μL, and hemoglobin \< 9 g/dL (NOTE: subject may not have received any growth factors or blood transfusions within seven days of the hematologic laboratory values obtained at the Screening visit)
- •Total bilirubin (TBL), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal
- •Creatinine (Cr) \> 2 mg/dL
- •Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide), 5-α reductase inhibitors (finasteride, dutasteride), estrogens, chemotherapy, or biologic therapy within 4 weeks of Day 1 visit
- •Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) of Day 1 visit, or radionuclide therapy within 8 weeks of Day 1
- •Planned palliative procedures for alleviation of bone pain such as radiation therapy or surgery
- •Structurally unstable bone lesions suggesting impending fracture
- •History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (Day 1 visit)
- •Clinically significant cardiovascular disease including:
Arms & Interventions
Enzalutamide + Abiraterone + Prednisone
Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.
Intervention: enzalutamide
Enzalutamide + Abiraterone + Prednisone
Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.
Intervention: abiraterone acetate
Enzalutamide + Abiraterone + Prednisone
Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.
Intervention: prednisone
Outcomes
Primary Outcomes
Number of Participants With Adverse Events (AEs)
Time Frame: From the first dose of study drug administration up 30 days following the last dose of study drug date, with a median duration of treatment of 10.1 months.
A treatment-emergent adverse event (TEAE) was defined as an adverse event occurring or worsening between the start of study treatment date and the latest date of 30 days after the last dose date or the 30-day follow-up visit date, and not later than the data cut-off date or the date of death. AEs, including abnormal clinical laboratory values, were graded using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) guidelines (V4.03).
Secondary Outcomes
- Change From Baseline in Testosterone Concentration in Bone Marrow Aspirate(Baseline and Week 9)
- Change From Baseline in Dihydrotestosterone (DHT) Concentration in Bone Marrow Aspirate(Baseline and Week 9)
- Change From Baseline in Cortisol in Bone Marrow Aspirate(Baseline and Week 9)
- Change From Baseline in Androstenedione in Bone Marrow Aspirate(Baseline and Week 9)
- Change From Baseline in Progesterone in Bone Marrow Aspirate(Baseline and Week 9)
- Change From Baseline in Pregnenolone in Bone Marrow Aspirate(Baseline and Week 9)
- Change From Baseline in Androstenedione Concentration in Blood(Baseline and Week 9)
- Change From Baseline in Pregnenolone Concentration in Blood(Baseline and Week 9)
- Change From Baseline in Testosterone Concentration in Blood(Baseline and Week 9)
- Change From Baseline in DHT Concentration in Blood(Baseline and Week 9)
- Change From Baseline in Cortisol Concentration in Blood(Baseline and Week 9)
- Change From Baseline in Progesterone Concentration in Blood(Baseline and Week 9)
- Change From Baseline to End-of-Treatment (EoT) in Prostate-Specific Antigen (PSA) Levels(Baseline and EoT; the median duration of treatment was 10.1 months.)
- Progression Free Survival (PFS)(Up to 1849 days)
- Percentage of Participants With Objective Response for Soft Tissue Lesions According to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST)(Up to 1849 days)
- Bone Scan Response at EoT(EoT; the median duration of treatment was 10.1 months.)
- Change From Baseline to EoT in Bone Specific Alkaline Phosphatase(Baseline and EoT; the median duration of treatment was 10.1 months.)
- Change From Baseline in Urine N-Telopeptide(Baseline and Week 9)