Clinical trial NCT01664923: Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: prostate cancer
enzalutamide
MDV3100
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Astellas Pharma Inc
name: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
First posted: 2012-08-14
Enrollment: 396
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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 outcomes:
measure: Time to PSA Progression
timeFrame: 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.
measure: Percentage of Participants With a PSA Response ≥ 50%
timeFrame: 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.
measure: Duration of Radiographic PFS
timeFrame: 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.
measure: Quality of Life: Time to Degradation of Functional Assessment of Cancer Therapy - Prostate (FACT-P)
timeFrame: 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.
measure: Best Overall Soft Tissue Response
timeFrame: 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.
measure: Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of study drug until the end of open label phase (up to maximum duration of 65 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham，IDS Pharmacy
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Desert Springs Cancer Care
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, PC
state: Arizona
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, PC
state: Arizona
city: Anaheim
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Antioch
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Antioch
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Fairfield
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Gilroy
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Los Angeles
country: United States
facility: Tower Urology
state: California
city: Los Angeles
country: United States
facility: UCLA Clark Urology Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Pharmaceutical Services
state: California
city: Martinez
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Milpitas
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Modesto
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Moutain View
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Napa
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Pleasanton
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Redwood City
country: United States
facility: Kaiser Permanente Medical Center Lab Drawing Station
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Bernardino
country: United States
facility: San Bernardino Urological Associates Medical Group
state: California
city: San Diego
country: United States
facility: Southern California Permanente Medical Group
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Jose
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Marcos
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Sherman Oaks
country: United States
facility: Skyline Urology
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Stanford
country: United States
facility: Standford Health Care
state: California
city: Torrance
country: United States
facility: Skyline Urology
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Center Pavilion Pharmacy
state: Colorado
city: Aurora
country: United States
facility: Anschutz Inpatient Pavilion
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Cancer Center, Anschutz Cancer Pavilion
state: Colorado
city: Denver
country: United States
facility: The Urology Center of Colorado
state: Colorado
city: Washington
country: United States
facility: George Washington University - Medical Faculty Associates
state: District of Columbia
city: Daytona Beach
country: United States
facility: Advanced Urology institute
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: East Coast Institute for Research, LLC
state: Florida
city: Naples
country: United States
facility: Specialists In Urology
state: Florida
city: Jeffersonville
country: United States
facility: First Urology, PSC
state: Indiana
city: Metairie
country: United States
facility: Metairie Oncologist, LLC
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: Regional Urology, LLC
state: Louisiana
city: Towson
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Troy
country: United States
facility: Michigan Institute of Urology
state: Michigan
city: Edina
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Creve Coeur
country: United States
facility: Barnes-Jewish West County Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University Infusion Center Pharmacy
state: Missouri
city: Saint Louis
country: United States
facility: Washington University, School of Medicine, 7th Floor, Center for Advanced Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Omaha
country: United States
facility: GU Research network,LLC / Urology Cancer Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley PC
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY, PLLC
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center-Steelcreek
state: North Carolina
city: Concord
country: United States
facility: Carolina Clinical Trials, LLC
state: North Carolina
city: Concord
country: United States
facility: Carolina Urology Partners, PLLC
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Durham
country: United States
facility: Investigational Chemotherapy Services
state: North Carolina
city: Greensboro
country: United States
facility: Alliance Urology Specialists, PA
state: North Carolina
city: Salisbury
country: United States
facility: Rowan Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health Urology
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Cincinnati
country: United States
facility: TriState Urologic Services PSC Inc., dba The Urology Group
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute
state: Ohio
city: Florence
country: United States
facility: Peace Harbor Hospital
state: Oregon
city: Salem
country: United States
facility: Salem Hospital
state: Oregon
city: Springfield
country: United States
facility: Oregon Urology Institute
state: Oregon
city: Springfield
country: United States
facility: Sacred Heart Nuclear Medicine
state: Oregon
city: Lancaster
country: United States
facility: Lancaster Urology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Medical Oncology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Urology Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center Hillman Cancer Center
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Physician Group
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Health
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates, PA
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates P.C.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Urology Clinics of North Texas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Texas Oncology-Memorial City
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah/Huntsman Cancer Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah/Huntsman Cancer Institute
state: Utah
city: Hampton
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Virginia Beach
country: United States
facility: Urology of Virginia, PLLC.
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Clinical Sciences Center
state: Wisconsin
Study officials:
affiliation: Pfizer
name: Pfizer Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Penson DF, Armstrong AJ, Concepcion RS, Agarwal N, Olsson CA, Karsh LI, Dunshee CJ, Duggan W, Shen Q, Sugg J, Haas GP, Higano CS. Enzalutamide versus bicalutamide in patients with nonmetastatic castration-resistant prostate cancer: a prespecified subgroup analysis of the STRIVE trial. Prostate Cancer Prostatic Dis. 2022 Feb;25(2):363-365. doi: 10.1038/s41391-021-00465-7. Epub 2021 Oct 7.
citation: Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, Dunshee C, Wang F, Wu K, Krivoshik A, Phung D, Higano CS. Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol. 2016 Jun 20;34(18):2098-106. doi: 10.1200/JCO.2015.64.9285. Epub 2016 Jan 25.