Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer
- Registration Number
- NCT01664923
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to determine the safety and efficacy of enzalutamide vs bicalutamide in asymptomatic or mildly symptomatic patients with prostate cancer who have disease progression despite primary androgen deprivation therapy.
- Detailed Description
This study is a multicenter phase 2, randomized, double-blind, efficacy and safety study of enzalutamide (160 mg/day) vs. bicalutamide (50 mg/day) in patients with recurrent prostate cancer who have serologic and/or radiographic disease progression despite primary androgen deprivation therapy.
Throughout the study, safety and tolerability will be assessed by the recording of adverse events, monitoring of vital signs, physical examinations, and safety laboratory evaluations.
Following study unblinding, study patients receiving enzalutamide or bicalutamide at the time of unblinding and qualifying patients randomized to bicalutamide who discontinued prior to unblinding will be offered the opportunity to receive open label enzalutamide treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 396
- Males age 18 or older;
- Histologically or cytologically confirmed adenocarcinoma of the prostate;
- Ongoing androgen deprivation therapy;
- Serum testosterone level ≤ 50 ng/dL (1.73 nmol/L) at the Screening visit;
- Progressive disease at study entry defined by prostate-specific antigen (PSA) progression and/or radiographic progression that occurred while the patient was on primary androgen deprivation therapy;
- Asymptomatic or mildly symptomatic from prostate cancer;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- Estimated life expectancy of ≥ 12 months;
- Able to swallow the study drug and comply with study requirements.
- Severe concurrent disease, infection, or co-morbidity;
- Known or suspected brain metastasis or active leptomeningeal disease;
- History of another invasive malignancy within the previous 5 years other than treated non-melanomatous skin cancer and American Joint Committee on Cancer (AJCC) Stage 0 or Stage 1 cancers that have a remote probability of recurrence;
- Absolute neutrophil count < 1,500/µL, or platelet count < 100,000/µL, or hemoglobin < 9 g/dL at the Screening visit;
- Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal (ULN) at the Screening visit;
- Creatinine > 2 mg/dL at the Screening visit;
- Albumin < 3.0 g/dL at the Screening visit;
- History of seizure or any condition that may predispose to seizure;
- Clinically significant cardiovascular disease;
- Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months);
- Major surgery within 4 weeks of enrollment;
- Use of opiate analgesics for pain from prostate cancer within 4 weeks of enrollment;
- Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment;
- Prior radiation or radionuclide therapy for treatment of distant metastases;
- Prior ketoconazole, abiraterone, or cytotoxic chemotherapy for prostate cancer;
- Treatment with hormonal therapy or biologic therapy for prostate cancer within 4 weeks of enrollment;
- Use of antiandrogens within 4 weeks prior to enrollment;
- Prior disease progression, as assessed by the Investigator, while receiving bicalutamide;
- Participation in a previous clinical trial of enzalutamide or an investigational agent that inhibits the androgen receptor or androgen synthesis (patients who received placebo are acceptable);
- Use of an investigational agent within 4 weeks of enrollment;
- Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids for prostate cancer within 4 weeks of enrollment;
- Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data.
Open-Label Treatment Period:
Inclusion Criteria:
-
Received randomized double blind treatment in MDV3100-09 as follows:
- Randomized to enzalutamide and receiving enzalutamide at the time of study unblinding;
- Randomized to bicalutamide and receiving bicalutamide at the time of study unblinding;
- Randomized to bicalutamide and discontinued bicalutamide before study unblinding;
-
Willing to maintain androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy.
Exclusion Criteria:
- Is currently or has taken commercially available enzalutamide (Xtandi) prior to participation in this open-label extension;
- Discontinued enzalutamide during the double-blind portion of the study prior to unblinding;
- Has any clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, infectious, metabolic, neurologic, psychiatric, psychologic, pulmonary, or renal disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator or medical monitor;
- Has a current or previously treated brain metastasis or leptomeningeal disease;
- Has a history of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma);
- Has a history of loss of consciousness or transient ischemic attack within 12 months of open label day 1;
- Has taken cytotoxic chemotherapy or investigational therapy within 4 weeks before enrollment (open label day 1).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enzalutamide Enzalutamide Enzalutamide 160 mg/day orally Bicalutamide Bicalutamide 50 mg/day orally
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm. PFS was defined as time from randomization to earliest objective evidence of prostate specific-antigen (PSA) progression, radiographic progression, or death on study. PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment. Radiographic progression in bone was based on The Prostate Cancer Clinical Trials Working Group (PCWG2) guidelines defined as at least 2 new lesions on bone scan. Radiographic progression in soft tissue on Computerized Tomography/Magnetic Resonance Imaging (CT/MRI) was based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had a PFS event at the time of the analysis data cutoff were censored at the date of last assessment.
- Secondary Outcome Measures
Name Time Method Duration of Radiographic PFS From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm. Duration of radiographic PFS was defined as the time from randomization to the earliest objective evidence of radiographic disease progression or death on study and was to be evaluated for participants with metastatic disease at study entry. Radiographic disease progression in bone was based on PCWG2 guidelines defined as at least 2 new lesions on bone scan. Radiographic disease progression in soft tissue on CT/MRI was based on RECIST 1.1. CT/MRI and bone scans were read locally by the same radiologist (or nuclear medicine physician for interpretation of bone scans) whenever possible. Participants not known to have had radiographic progression at the time of analysis data cutoff were censored at the date of last radiographic assessment.
Percentage of Participants With a PSA Response ≥ 50% From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm. PSA response was defined as a reduction in PSA of at least 50% from baseline at any post baseline assessment confirmed by a second PSA assessment at least 3 weeks later.
Quality of Life: Time to Degradation of Functional Assessment of Cancer Therapy - Prostate (FACT-P) From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm. The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess patient function in 4 domains: physical, social/family, emotional, and functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score (0 to 156) with higher scores representing better quality of life. Time to degradation of FACT-P was defined as the time from randomization to first assessment with at least a 10-point decrease from baseline in the global FACT-P score for each participant. Participants with no score degradation at the time of analysis data cutoff were censored at the date of last assessment showing no degradation.
Best Overall Soft Tissue Response From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm. Best overall soft tissue response is defined as partial response (PR) or complete response (CR) while on study treatment based on investigator assessment of target, nontarget, and new lesions using RECIST 1.1. Only participants in the metastatic population with measurable soft tissue disease (at least 1 target lesion identified per RECIST 1.1) at screening were included in the analysis. All percentages are based on number of participants with metastatic and measurable soft tissue disease at screening in each treatment group.
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) From first dose of study drug until the end of open label phase (up to maximum duration of 65 months) An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. A treatment emergent AE defined as an event that emerged during treatment period (From first dose of study drug until end of open label phase \[up to maximum duration of 65 months\]) that was absent before treatment, or worsened during treatment period relative to pre-treatment state. AE included both serious and non- SAE. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was considered related to study drug if event was assessed by investigator as probably or possibly related.
Time to PSA Progression From randomization until the data cut-off date of 09 February 2015, median duration of treatment was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm. PSA progression was defined as ≥ 25% increase in PSA with an absolute increase ≥ 2 ng/mL above the nadir and was to be confirmed by a second consecutive assessment at least 3 weeks later. Participants not known to have had PSA progression were censored at the date of last PSA assessment.
Trial Locations
- Locations (80)
Alliance Urology Specialists, PA
🇺🇸Greensboro, North Carolina, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
UCLA Clark Urology Clinic
🇺🇸Los Angeles, California, United States
East Coast Institute for Research, LLC
🇺🇸Jacksonville, Florida, United States
Tower Urology
🇺🇸Los Angeles, California, United States
UCLA Department of Pharmaceutical Services
🇺🇸Los Angeles, California, United States
Associated Medical Professionals of NY, PLLC
🇺🇸Syracuse, New York, United States
Kaiser Permanente Medical Center Lab Drawing Station
🇺🇸Redwood City, California, United States
Specialists In Urology
🇺🇸Naples, Florida, United States
San Bernardino Urological Associates Medical Group
🇺🇸San Bernardino, California, United States
Michigan Institute of Urology
🇺🇸Troy, Michigan, United States
Rowan Regional Medical Center
🇺🇸Salisbury, North Carolina, United States
Skyline Urology
🇺🇸Torrance, California, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Advanced Urology institute
🇺🇸Daytona Beach, Florida, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Chesapeake Urology Research Associates
🇺🇸Towson, Maryland, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Woodbury, Minnesota, United States
AccuMed Research Associates
🇺🇸Garden City, New York, United States
Washington University, School of Medicine, 7th Floor, Center for Advanced Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Barnes-Jewish West County Hospital
🇺🇸Creve Coeur, Missouri, United States
Salem Hospital
🇺🇸Salem, Oregon, United States
Carolina Urology Partners, PLLC
🇺🇸Concord, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Peace Harbor Hospital
🇺🇸Florence, Oregon, United States
Cleveland Clinic Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
Texas Oncology-Memorial City
🇺🇸Houston, Texas, United States
Southern California Permanente Medical Group
🇺🇸San Marcos, California, United States
Kaiser Permanente Medical Center
🇺🇸Walnut Creek, California, United States
Standford Health Care
🇺🇸Stanford, California, United States
First Urology, PSC
🇺🇸Jeffersonville, Indiana, United States
Regional Urology, LLC
🇺🇸Shreveport, Louisiana, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University Infusion Center Pharmacy
🇺🇸Saint Louis, Missouri, United States
Premier Medical Group of the Hudson Valley PC
🇺🇸Poughkeepsie, New York, United States
Carolinas Medical Center-Steelcreek
🇺🇸Charlotte, North Carolina, United States
Carolina Clinical Trials, LLC
🇺🇸Concord, North Carolina, United States
Jefferson Medical Oncology
🇺🇸Philadelphia, Pennsylvania, United States
Jefferson Urology Associates
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Mount Nittany Health
🇺🇸State College, Pennsylvania, United States
UPMC Cancer Center Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Urology Clinics of North Texas
🇺🇸Dallas, Texas, United States
Urology of Virginia, PLLC.
🇺🇸Virginia Beach, Virginia, United States
University of Wisconsin Clinical Sciences Center
🇺🇸Madison, Wisconsin, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
TriState Urologic Services PSC Inc., dba The Urology Group
🇺🇸Cincinnati, Ohio, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Investigational Chemotherapy Services
🇺🇸Durham, North Carolina, United States
Urology San Antonio Research
🇺🇸San Antonio, Texas, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Colorado Cancer Center, Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
University of Alabama at Birmingham，IDS Pharmacy
🇺🇸Birmingham, Alabama, United States
Anschutz Cancer Center Pavilion Pharmacy
🇺🇸Aurora, Colorado, United States
University of Utah/Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Anschutz Inpatient Pavilion
🇺🇸Aurora, Colorado, United States
The Urology Center of Colorado
🇺🇸Denver, Colorado, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Utah/Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
GU Research network,LLC / Urology Cancer Center
🇺🇸Omaha, Nebraska, United States
George Washington University - Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Oregon Urology Institute
🇺🇸Springfield, Oregon, United States
Mount Nittany Physician Group
🇺🇸State College, Pennsylvania, United States
Arizona Oncology Associates, PC - HOPE
🇺🇸Tucson, Arizona, United States
Desert Springs Cancer Care
🇺🇸Scottsdale, Arizona, United States
Urology Associates P.C.
🇺🇸Nashville, Tennessee, United States
Charleston Hematology Oncology Associates, PA
🇺🇸Charleston, South Carolina, United States
Metairie Oncologist, LLC
🇺🇸Metairie, Louisiana, United States
Carolina Urologic Research Center
🇺🇸Myrtle Beach, South Carolina, United States
Urological Associates of Southern Arizona, PC
🇺🇸Tucson, Arizona, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Sacred Heart Nuclear Medicine
🇺🇸Springfield, Oregon, United States
Wake Forest Baptist Health Urology
🇺🇸Winston-Salem, North Carolina, United States
Lancaster Urology
🇺🇸Lancaster, Pennsylvania, United States