A Study to Determine Safety and Tolerability of Enzalutamide (MDV3100) in Combination With Abiraterone Acetate in Bone Metastatic Castration-Resistant Prostate Cancer Patients

NCT01650194 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 9785-CL-0011
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

abiraterone acetate; prednisone; enzalutamide; cancer; prostate; MDV3100

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs)

  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).

  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.

Secondary Outcomes (18)

• 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

Other Outcomes (1)

• Androgen Receptor Signaling Assessed by Expression and Localization of Androgen Receptor (AR), CYP17 Expression, Splice Variants, and Pathways Linked With Non-classical AR Signaling and Bone Development

  Baseline and Week 9

Study Arms (1)

Enzalutamide + Abiraterone + Prednisone

EXPERIMENTAL

Participants received enzalutamide combined with abiraterone acetate once daily plus prednisone twice daily.

Drug: enzalutamide; Drug: abiraterone acetate; Drug: prednisone

Interventions

enzalutamide DRUG

Participants received 160 mg of enzalutamide orally once daily (4 capsules, 40 mg each).

Also known as: MDV3100

Enzalutamide + Abiraterone + Prednisone

abiraterone acetate DRUG

Participants received 1000 mg of abiraterone acetate orally once daily (4 tablets, 250 mg each).

Enzalutamide + Abiraterone + Prednisone

prednisone DRUG

Participants received 5 mg of prednisone orally twice daily (2 tablets, 5 mg each).

Enzalutamide + Abiraterone + Prednisone

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Agree to use a double-barrier method of contraception which involves the use of a condom in combination with one of the following: contraceptive sponge, diaphragm, or cervical ring with spermicidal gel or foam, if having sex with a woman of child-bearing potential during the length of the study and for one week after abiraterone is discontinued and for at least three months after enzalutamide is discontinued
• Subject agrees not to participate in another interventional study while on treatment

You may not qualify if:

• 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:
• Myocardial infarction within 6 months of Screening visit;
• Uncontrolled angina within 3 months of Screening visit;
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the Screening visit results in a left ventricular ejection fraction that is ≥ 45%
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes)
• Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the Electrocardiogram (ECG) \> 470 msec.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Medivation LLC, a wholly owned subsidiary of Pfizer Inc.: collaborator

Study Sites (1)

Site US2492 MD Anderson Cancer Ctr

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Assi R, Temraz S, Shamseddine A, Mukherji D. New Compounds Targeting the Androgen Receptor for Treatment of Advanced Prostate Cancer. Curr Drug Targets. 2016;17(3):290-302. doi: 10.2174/1389450116666150907101044.

  PMID: 26343110 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Neoplasms

Interventions

enzalutamide; Abiraterone Acetate; Prednisone

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Astellas Pharma Global Development, Inc. (APGD)

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Associate Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2012
• First Posted: July 26, 2012
• Study Start: July 9, 2012
• Primary Completion: January 4, 2018
• Study Completion: January 4, 2018
• Last Updated: December 10, 2024
• Results First Posted: February 5, 2019

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

US (1)