A Phase III, Randomized, Efficacy and Safety Study of Enzalutamide Plus Leuprolide, Enzalutamide Monotherapy, and Placebo Plus Leuprolide in Men With High-risk Nonmetastatic Prostate Cancer Progressing After Definitive Therapy

Study Identifier:
MDV3100-13
CT.gov Identifier:
NCT02319837
EudraCT Identifier:
2014-001634-28
EU Trial (CTIS) Number:
2024-513521-23-00
Study Contact Information:
(210) 593-5651 or [email protected]
Study Complete

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Study Summary

To evaluate the efficacy and safety of enzalutamide in patients with high-risk, hormone-sensitive, non-metastatic prostate cancer that has biochemically recurred (rising prostate-specific antigen [PSA] level) following definitive local therapy with radical prostatectomy and/or radiation therapy.

To determine if enzalutamide can delay the development of metastatic prostate cancer in high-risk men with a rapidly rising PSA.

To assess enzalutamide plus leuprolide in patients with high-risk nonmetastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both.

To assess Tx effects in time to first and confirmed (at next visit) clinically meaningful deterioration (TTFD/TTFCD) as measured with the Brief Pain Inventory Short Form (BPI-SF) worst pain and Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score using predefined thresholds.

To present other non-key secondary efficacy endpoints for enza monotherapy vs placebo + LA.

All efficacy objectives will compare enzalutamide plus leuprolide and enzalutamide monotherapy versus placebo plus leuprolide.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Prostate
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    III
    Sex
    Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Enzalutamide plus leuprolide
    • Read More
  • Drug: Experimental: Enzalutamide monotherapy
  • Drug: Active Comparator: Placebo plus leuprolide
  • Drug: The randomized blinded portion of the study has concluded following primary endpoint analyses. In the Open Label Period the placebo is no longer applicable in this study arm, and patients continue to receive leuprolide alone.
  • Drug: Drug: Placebo (No longer applicable in Open Label study period)
  • Drug: ESMO 2020:
  • Drug: Enzalutamide plus leuprorelin (enzalutamide combination arm) (n=355), placebo plus leuprorelin ( placebo (n=358) or enzalutamide monotherapy (n=355)
  • Drug: Subjects were administered daily enzalutamide 160 mg and leuprorelin (enzalutamide combination group), enzalutamide 160 mg as monotherapy (enzalutamide monotherapy group), placebo and leuprorelin (placebo group) at random. Leuprorelin was administered at 22.5 mg every 12 weeks.
  • Drug: ASTRO 2023
  • Drug: Pts were randomized 1: 1 to enza 160 mg/day + leuprolide (22.5 mg every 12 weeks) or leuprolide alone. Tx was suspended at week 37 if serum PSA was <0.2 ng/mL at week 36 and restarted when PSA reached ≥2 ng/mL (primary RP) or ≥5 ng/mL (no primary RP).
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Study Complete

    Requirements information
    Inclusion criteria
    • Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features;
    • Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent;
    • PSA doubling time < or = 9 months;
    • Screening PSA by the central laboratory > or = 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer;
    • Serum testosterone < or = 150 ng/dL (5.2 nmol/L).
    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
    • Estimated life expectancy of >or= 12 months.
    • Able to swallow the study drug and comply with study requirements including independently completing study questionnaires.
    • Throughout study, the patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) from screening through 3 months after the last dose of study drug or per local guidelines where these require additional description of contraceptive methods. Two acceptable methods of birth control thus include the following:
    • Condom (barrier method is required)
    • One of the following is required:
    • Established and ongoing use of oral, injected, or implanted hormonal method of contraception by the female partner
    • Placement of an intrauterine device or intrauterine system by the female partner
    • Additional barrier method including contraceptive sponge and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner
    • Tubal ligation in the female partner performed at least 6 months before screening
    • Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), performed at least 6 months before screening
    • Throughout the study, the patient must use a condom if having sex with a pregnant woman.
    • Must agree not to donate sperm from first dose of study drug through 3 months after the last dose of study drug.
    • Subjects must fulfil the following entry criteria indicative of having biochemical relapse and high-risk disease: PSA doubling time < or = 9 months; screening PSA threshold of > or = 2.0 ng/mL for subjects who had prior radical prostatectomy or > or = 5.0 ng/mL and > or = nadir + 2 ng/mL for subjects who had radiotherapy as the primary therapy; androgen deprivation therapy < or = 36 months in duration and > or = 9 months before randomization and administered only in the neoadjuvant/adjuvant setting;
    • Treatment will be reinitiated if PSA values rise > or = 2.0 ng/mL for patients with prior prostatectomy or > or = 5.0 ng/mL for those with only prior radiotherapy.
    • Age 18 years or older and willing and able to provide informed consent
    Exclusion criteria
    • Prior or present evidence of distant metastatic disease as assessed by radiographic imaging;
    • Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer < or = 36 months in duration and > or = 9 months before randomization, or a single dose or a short course (< or = 6 months) of hormonal therapy given for rising PSA > or = 9 months before randomization is allowed.;
    • Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer;
    • Prior systemic biologic therapy, including immunotherapy, for prostate cancer;
    • Major surgery within 4 weeks before randomization;
    • Treatment with 5-a reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization;
    • Known or suspected brain metastasis or active leptomeningeal disease;
    • History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruiting
    Condition(s) Treated at Site
    Prostate