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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Medivation, Inc.
ClinicalTrials.gov Identifier:
NCT01664923
First received: August 10, 2012
Last updated: May 9, 2016
Last verified: May 2016

August 10, 2012
May 9, 2016
August 2012
February 2015   (final data collection date for primary outcome measure)
Progression Free Survival (PFS) [ Time Frame: 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. ] [ Designated as safety issue: No ]
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.
Progression Free Survival (PFS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01664923 on ClinicalTrials.gov Archive Site
  • Time to PSA Progression [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.
  • Percentage of Participants With a PSA Response ≥ 50% [ Time Frame: 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. ] [ Designated as safety issue: No ]
    PSA response was defined as a reduction in PSA of at least 50% from baseline at any postbaseline assessment confirmed by a second PSA assessment at least 3 weeks later.
  • Duration of Radiographic PFS [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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.
  • Quality of Life: Time to Degradation of Functional Assessment of Cancer Therapy - Prostate (FACT-P) [ Time Frame: 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. ] [ Designated as safety issue: No ]

    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 [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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 Adverse Event (AE) [ Time Frame: From first dose of study drug up to 30 days after last dose of study drug. Median duration of the AE reporting period was 15.2 months in the enzalutamide arm and 9.4 months in the bicalutamide arm. ] [ Designated as safety issue: Yes ]

    Assessment of adverse events was conducted from the date and time of the first dose of study drug through 30 days after the date of the last dose of study drug or before initiation of a cytotoxic or investigational therapy, whichever occurred first.

    A serious adverse event was defined as any untoward medical occurrence that:

    • Resulted in death;
    • Was life threatening;
    • Required inpatient hospitalization or led to prolongation of hospitalization;
    • Resulted in persistent or significant disability or incapacity;
    • Resulted in a congenital anomaly or birth defect;
    • Was a medically important event.

    An adverse event was considered related to the study drug if the event was assessed by the investigator as probably or possibly related.

  • Time to Prostate Specific Antigen (PSA) Progression [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • PSA Response [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
  • Time to Radiographic Progression [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
  • Functional Assessment of Cancer Therapy - Prostate (FACT-P) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Safety assess by AEs, frequency of study drug discontinuation due to AEs, laboratory evaluations and vital signs
Not Provided
Not Provided
 
Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer
A Multicenter Phase 2, Randomized, Double-Blind, Efficacy and Safety Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer Who Have Failed Primary Androgen Deprivation Therapy
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Prostate Cancer
  • Drug: Enzalutamide
    160 mg, daily, by mouth.
    Other Names:
    • MDV3100
    • Xtandi
  • Drug: Bicalutamide
    50 mg, daily, by mouth
    Other Name: Casodex
  • Experimental: Enzalutamide
    Enzalutamide 160 mg/day orally
    Intervention: Drug: Enzalutamide
  • Active Comparator: Bicalutamide
    50 mg/day orally
    Intervention: Drug: Bicalutamide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
396
June 2018
February 2015   (final data collection date for primary outcome measure)

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).
Male
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01664923
MDV3100-09
Not Provided
Not Provided
Not Provided
Medivation, Inc.
Medivation, Inc.
Astellas Pharma Inc
Study Director: Medical Director Medivation, Inc.
Medivation, Inc.
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP