Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer

Prostate Cancer Clinical Trial

— STRIVE  

Official title:

STRIVE: A MULTICENTER PHASE 2, RANDOMIZED, DOUBLE-BLIND, EFFICACY AND SAFETY STUDY OF ENZALUTAMIDE VS. BICALUTAMIDE IN MEN WITH PROSTATE CANCER WHO HAVE FAILED PRIMARY ANDROGEN DEPRIVATION THERAPY

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01664923
• Other study ID #: MDV3100-09
• Secondary ID: C3431014
• Status: Completed
• Phase: Phase 2
• Start date: August 2012
• Est. completion date: January 2018

Study information

• Verified date: January 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 396
• Est. completion date: January 2018
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
160 mg, daily, by mouth.
• Bicalutamide
50 mg, daily, by mouth

Locations

Country	Name	City	State
United States	Southern California Permanente Medical Group	Anaheim	California
United States	Kaiser Permanente Medical Center Lab Drawing Station	Antioch	California
United States	Kaiser Permanente Medical Center Lab Drawing Station	Antioch	California
United States	Anschutz Cancer Center Pavilion Pharmacy	Aurora	Colorado
United States	Anschutz Inpatient Pavilion	Aurora	Colorado
United States	University of Colorado Cancer Center, Anschutz Cancer Pavilion	Aurora	Colorado
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Alabama at Birmingham,IDS Pharmacy	Birmingham	Alabama
United States	Charleston Hematology Oncology Associates, PA	Charleston	South Carolina
United States	Carolinas Medical Center-Steelcreek	Charlotte	North Carolina
United States	TriState Urologic Services PSC Inc., dba The Urology Group	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Institute	Cleveland	Ohio
United States	Carolina Clinical Trials, LLC	Concord	North Carolina
United States	Carolina Urology Partners, PLLC	Concord	North Carolina
United States	Barnes-Jewish West County Hospital	Creve Coeur	Missouri
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Urology Clinics of North Texas	Dallas	Texas
United States	Advanced Urology institute	Daytona Beach	Florida
United States	The Urology Center of Colorado	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Investigational Chemotherapy Services	Durham	North Carolina
United States	Minnesota Oncology Hematology, P.A.	Edina	Minnesota
United States	Kaiser Permanente Medical Center Lab Drawing Station	Fairfield	California
United States	Peace Harbor Hospital	Florence	Oregon
United States	AccuMed Research Associates	Garden City	New York
United States	Kaiser Permanente Medical Center Lab Drawing Station	Gilroy	California
United States	Alliance Urology Specialists, PA	Greensboro	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Virginia Oncology Associates	Hampton	Virginia
United States	Texas Oncology-Memorial City	Houston	Texas
United States	East Coast Institute for Research, LLC	Jacksonville	Florida
United States	East Coast Institute for Research, LLC	Jacksonville	Florida
United States	First Urology, PSC	Jeffersonville	Indiana
United States	Lancaster Urology	Lancaster	Pennsylvania
United States	Southern California Permanente Medical Group	Los Angeles	California
United States	Tower Urology	Los Angeles	California
United States	UCLA Clark Urology Clinic	Los Angeles	California
United States	UCLA Department of Pharmaceutical Services	Los Angeles	California
United States	University of Wisconsin Clinical Sciences Center	Madison	Wisconsin
United States	Kaiser Permanente Medical Center Lab Drawing Station	Martinez	California
United States	Metairie Oncologist, LLC	Metairie	Louisiana
United States	Kaiser Permanente Medical Center Lab Drawing Station	Milpitas	California
United States	Kaiser Permanente Medical Center Lab Drawing Station	Modesto	California
United States	Kaiser Permanente Medical Center Lab Drawing Station	Moutain View	California
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Kaiser Permanente Medical Center Lab Drawing Station	Napa	California
United States	Specialists In Urology	Naples	Florida
United States	Urology Associates P.C.	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Kaiser Permanente Medical Center	Oakland	California
United States	GU Research network,LLC / Urology Cancer Center	Omaha	Nebraska
United States	Jefferson Medical Oncology	Philadelphia	Pennsylvania
United States	Jefferson Urology Associates	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	UPMC Cancer Center Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Medical Center Lab Drawing Station	Pleasanton	California
United States	Premier Medical Group of the Hudson Valley PC	Poughkeepsie	New York
United States	Kaiser Permanente Medical Center Lab Drawing Station	Redwood City	California
United States	Kaiser Permanente Medical Center	Roseville	California
United States	Kaiser Permanente Medical Center	Sacramento	California
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	UC Davis Medical Center	Sacramento	California
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University Infusion Center Pharmacy	Saint Louis	Missouri
United States	Washington University, School of Medicine, 7th Floor, Center for Advanced Medicine	Saint Louis	Missouri
United States	Salem Hospital	Salem	Oregon
United States	Rowan Regional Medical Center	Salisbury	North Carolina
United States	University of Utah/Huntsman Cancer Hospital	Salt Lake City	Utah
United States	University of Utah/Huntsman Cancer Institute	Salt Lake City	Utah
United States	Urology San Antonio Research	San Antonio	Texas
United States	San Bernardino Urological Associates Medical Group	San Bernardino	California
United States	Southern California Permanente Medical Group	San Diego	California
United States	Kaiser Permanente Medical Center	San Francisco	California
United States	Kaiser Permanente Medical Center	San Jose	California
United States	Kaiser Permanente Medical Center	San Leandro	California
United States	Southern California Permanente Medical Group	San Marcos	California
United States	Kaiser Permanente Medical Center	Santa Clara	California
United States	Desert Springs Cancer Care	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Skyline Urology	Sherman Oaks	California
United States	Regional Urology, LLC	Shreveport	Louisiana
United States	Kaiser Permanente Medical Center	South San Francisco	California
United States	Oregon Urology Institute	Springfield	Oregon
United States	Sacred Heart Nuclear Medicine	Springfield	Oregon
United States	Standford Health Care	Stanford	California
United States	Mount Nittany Health	State College	Pennsylvania
United States	Mount Nittany Physician Group	State College	Pennsylvania
United States	Associated Medical Professionals of NY, PLLC	Syracuse	New York
United States	Skyline Urology	Torrance	California
United States	Chesapeake Urology Research Associates	Towson	Maryland
United States	Michigan Institute of Urology	Troy	Michigan
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Urological Associates of Southern Arizona, PC	Tucson	Arizona
United States	Urological Associates of Southern Arizona, PC	Tucson	Arizona
United States	Kaiser Permanente Medical Center	Vallejo	California
United States	Urology of Virginia, PLLC.	Virginia Beach	Virginia
United States	Kaiser Permanente Medical Center	Walnut Creek	California
United States	George Washington University - Medical Faculty Associates	Washington	District of Columbia
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina
United States	Wake Forest Baptist Health Urology	Winston-Salem	North Carolina
United States	Minnesota Oncology Hematology, P.A.	Woodbury	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Pfizer	Astellas Pharma Inc, Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	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.	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.
Secondary	Time to PSA Progression	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.	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.
Secondary	Percentage of Participants With a PSA Response = 50%	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.	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.
Secondary	Duration of Radiographic PFS	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.	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.
Secondary	Quality of Life: Time to Degradation of Functional Assessment of Cancer Therapy - Prostate (FACT-P)	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.	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.
Secondary	Best Overall Soft Tissue Response	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.	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.
Secondary	Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	From first dose of study drug until the end of open label phase (up to maximum duration of 65 months)