Clinical Trials /

A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer

NCT03085095

Description:

The purpose of this study is to determine the benefit and safety of relugolix 120 mg orally once daily for 48 weeks on maintaining serum testosterone suppression to castrate levels (≤ 50 ng/dL [1.7 nmol/L] in participants with androgen-sensitive advanced prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer
  • Official Title: HERO: A Multinational Phase 3 Randomized, Open-label, Parallel Group Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: MVT-601-3201
  • SECONDARY ID: 2017-000160-15
  • NCT ID: NCT03085095

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
RelugolixTAK-385Relugolix
Leuprolide AcetateLeuprolide Acetate

Purpose

The purpose of this study is to determine the benefit and safety of relugolix 120 mg orally once daily for 48 weeks on maintaining serum testosterone suppression to castrate levels (≤ 50 ng/dL [1.7 nmol/L] in participants with androgen-sensitive advanced prostate cancer.

Detailed Description

      This study is an international phase 3 randomized, open-label, parallel group efficacy and
      safety study to evaluate oral daily relugolix 120 mg in participants with androgen-sensitive
      advanced prostate cancer who require at least 1 year (48 weeks) of continuous androgen
      deprivation therapy. Relugolix 120 mg orally once daily or leuprolide acetate depot
      suspension, 22.5 mg (or 11.25 mg in some Asian countries), every 3-months by subcutaneous or
      intramuscular injection will be administered to participants with prostate cancer who require
      androgen deprivation therapy.

      Approximately 1100 participants will be enrolled in this study, including approximately 390
      participants with metastatic advanced prostate cancer to support the analysis of the
      secondary endpoint of time to castration-resistance and 138 Chinese participants (enrolled in
      China and Taiwan) to support registration in China. The study includes a Screening Period, a
      Treatment Period of 48 weeks, and a Follow-up Period. Additionally, unscheduled follow-up
      visit(s) may be arranged for participants with study-related safety concerns as needed.
      Eligible participants include those with evidence of biochemical relapse (rising
      prostate-specific antigen) following local primary intervention with curative intent, newly
      diagnosed metastatic disease (excluding metastases to the brain), and/or advanced localized
      disease.

      Following successful completion of the Screening period study participants will be randomized
      2:1 to oral relugolix 120 mg once daily or leuprolide acetate 22.5 mg (or 11.25 mg in some
      Asian countries) 3-month depot subcutaneous or intramuscular injection and will attend visits
      monthly (every 4 weeks) where serum testosterone and prostate-specific antigen will be
      assessed. Safety will be assessed throughout the study by monitoring adverse events, vital
      signs, physical examinations, clinical laboratory tests, and 12-lead electrocardiograms.
    

Trial Arms

NameTypeDescriptionInterventions
RelugolixExperimentalRelugolix 120 mg for 48 weeks
  • Relugolix
Leuprolide AcetateActive ComparatorLeuprolide acetate 22.5 mg (or 11.25 mg in some Asian countries) for 48 weeks
  • Leuprolide Acetate

Eligibility Criteria

        Key Inclusion Criteria:

          1. Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the
             prostate;

          2. Is a candidate for, in the opinion of the investigator, at least 1 year of continuous
             androgen deprivation therapy for the management of androgen-sensitive advanced
             prostate cancer with one of the following clinical disease state presentations:

               1. Evidence of biochemical (PSA) or clinical relapse following local primary
                  intervention with curative intent, such as surgery, radiation therapy,
                  cryotherapy, or high-frequency ultrasound and not a candidate for salvage
                  treatment by surgery; or

               2. Newly diagnosed androgen-sensitive metastatic disease; or

               3. Advanced localized disease unlikely to be cured by local primary intervention
                  with either surgery or radiation with curative intent

             Note: Once 915 participants are enrolled worldwide only participants with metastatic
             advanced prostate cancer will be eligible for the study in all regions except China,
             where both metastatic and non-metastatic participants will continue to be enrolled.

          3. Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nmol/L);

          4. Has a serum PSA concentration at the Screening visit of > 2.0 ng/mL (2.0 μg/L), or,
             when applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 μg/L) or post
             radiotherapy, cryotherapy, or high frequency ultrasound > 2.0 ng/mL (2.0 μg/L) above
             the post interventional nadir;

          5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at
             initial screening and at baseline.

        Key Exclusion Criteria:

          1. In the investigator's opinion, is likely to require chemotherapy or surgical therapy
             for symptomatic disease management within 2 months of initiating androgen deprivation
             therapy;

          2. Previously received gonadotropin-releasing hormone analog or other form of androgen
             deprivation therapy (estrogen or antiandrogen) for > 18 months total duration. If
             androgen deprivation therapy was received for ≤ 18 months total duration, then that
             therapy must have been completed at least 3 months prior to baseline. If the dosing
             interval of the depot is longer than 3 months, then the prior androgen deprivation
             therapy must have been completed at least as long as the dosing interval of the depot;

          3. Previous systemic cytotoxic treatment for prostate cancer (eg, taxane-based regimen);

          4. Metastases to brain per prior clinical evaluation;

          5. Scheduled for major surgery after baseline;

          6. History of surgical castration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Sustained Castration Rate
Time Frame:up to 48 weeks
Safety Issue:
Description:Sustained castration rate defined as the cumulative probability of testosterone suppression to ≤ 50 ng/dL (1.7 nmol/L) while on study treatment from Week 5 through Week 48

Secondary Outcome Measures

Measure:Castration Rate by Visit
Time Frame:up to 5 weeks
Safety Issue:
Description:Castration rate defined as the cumulative probability of testosterone suppression to ≤ 50 ng/dL (1.7 nmol/L).
Measure:Profound Castration Rate
Time Frame:up to 48 weeks
Safety Issue:
Description:Castration rate defined as the cumulative probability of testosterone suppression to ≤ 20 ng/dL (0.7 nmol/L) while on study treatment.
Measure:Prostate-specific Antigen (PSA) Response Rate by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) Criteria
Time Frame:at 3 weeks and at 5 weeks
Safety Issue:
Description:Proportion of participants with a confirmed PSA response by PCWG3 guidelines.
Measure:PSA Response Rate
Time Frame:up to 48 weeks
Safety Issue:
Description:Proportion of participants with PSA concentration < 0.2 ng/mL.
Measure:Time to PSA Progression
Time Frame:up to 48 weeks
Safety Issue:
Description:Time from baseline to PSA progression as defined by PCWG3 guidelines.
Measure:Quality of Life (QoL) Total Score and Each Subdomain Score
Time Frame:up to 48 weeks
Safety Issue:
Description:Assessed by the European Organisation of Research and Treatment of Cancer (EORTC)-QLQ-C30 and EORTC-QLQ-PR25 questionnaires.
Measure:QoL Total Score and Each Subdomain Score
Time Frame:up to 48 weeks
Safety Issue:
Description:Assessed by the European Quality of Life 5-Dimension 5-Level questionnaire.
Measure:Castration Resistance Free Survival
Time Frame:up to 48 weeks
Safety Issue:
Description:Defined as the time from the date of first dose to the date of PSA progression while castrated or death due to any reason, whichever occurs earlier.
Measure:Composite of Safety as Measure of Safety and Tolerability
Time Frame:up to 52 weeks
Safety Issue:
Description:Safety will be evaluated by the incidence of serious adverse events, incidence and severity of adverse events, incidence of permanent treatment discontinuation due to adverse events, and incidence of new clinically significant changes in clinical laboratory values and vital signs.
Measure:Pharmacokinetics of Relugolix
Time Frame:up to 48 weeks
Safety Issue:
Description:Blood samples will be collected from participants for measurement of plasma relugolix concentrations.
Measure:Serum Concentrations of Luteinizing Hormone, Follicle-Stimulating Hormone, Dihydrotestosterone, Sex Hormone-Binding Globulin
Time Frame:up to 61 weeks
Safety Issue:
Description:Blood samples will be collected from participants for hormonal measurements.
Measure:Testosterone Recovery
Time Frame:up to 90-days follow-up
Safety Issue:
Description:Blood samples will be collected from participants for serum testosterone measurements.
Measure:Sustained Profound Castration Rate
Time Frame:up to 48 weeks
Safety Issue:
Description:Sustained profound castration rate defined as the cumulative probability of testosterone suppression to ≤ 20 ng/dL (0.7 nmol/L) while on study treatment.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Myovant Sciences GmbH

Last Updated

November 7, 2019