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

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ClinicalTrials.gov Identifier: NCT03085095
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : October 29, 2020
Sponsor:
Information provided by (Responsible Party):
Myovant Sciences GmbH

Tracking Information
First Submitted Date  ICMJE March 9, 2017
First Posted Date  ICMJE March 21, 2017
Last Update Posted Date October 29, 2020
Actual Study Start Date  ICMJE April 18, 2017
Actual Primary Completion Date October 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 10, 2020)
Sustained Castration Rate [ Time Frame: From Week 5 Day 1 to Week 49 Day 1 ]
Sustained castration rate defined as the cumulative probability of testosterone suppression to < 50 ng/dL (1.7 nmol/L) for relugolix while on study treatment from Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337).
Original Primary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
Sustained Castration Rate [ Time Frame: 48 weeks ]
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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2020)
  • Castration Rate [ Time Frame: Week 1 Day 4 and Week 3 Day 1 ]
    Castration rate defined as the cumulative probability of testosterone suppression to < 50 ng/dL (1.7 nmol/L).
  • Confirmed Prostate-specific Antigen (PSA) Response Rate [ Time Frame: Week 3 Day 1 and Week 5 Day 1 ]
    Confirmed PSA response defined as > 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.
  • Profound Castration Rate [ Time Frame: Up to Week 3 Day 1 ]
    Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL (0.7 nmol/L) while on study treatment.
  • Follicle-Stimulating Hormone (FSH) Level [ Time Frame: Week 25 Day 1 ]
    To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.
  • Castration Resistance Free Survival In Participants With Metastatic Prostate Cancer [ Time Frame: Up to Week 49 Day 1 ]
    Defined as the time from the date of first dose to the date of confirmed PSA progression while castrated or death due to any reason, whichever occurs earlier. Formally tested in the final analysis only if the above endpoints are all positive in the primary analysis.
  • Castration Resistance Free Survival In Participants With Or Without Metastatic Prostate Cancer [ Time Frame: Up to Week 49 Day 1 ]
    Defined as the time from the date of first dose to the date of confirmed PSA progression while castrated or death due to any reason, whichever occurs earlier. Formally tested in the final analysis only if the above endpoints are all positive in the primary analysis.
  • Testosterone Recovery To 280 ng/dL [ Time Frame: At the 90-day follow-up ]
    Cumulative probability of testosterone recovery to 280 ng/dL at the 90-day follow-up in approximately 150 participants who complete 48 weeks of treatment and who do not plan to start alternative androgen deprivation therapy within the following 12 weeks (or within 24 weeks following the last injection of leuprolide acetate 3-month depot). Formally tested in the primary analysis population only if the above endpoints are all positive.
  • Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1 And Week 25 Day 1 Through Week 49 Day 1 [ Time Frame: Week 5 Day 1 and Week 25 Day 1 through Week 49 Day 1 ]
    Sustained profound castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL (0.7 nmol/L).
  • Undetectable PSA Rate [ Time Frame: Week 25 Day 1 ]
    Defined as the proportion of participants with PSA concentration < 0.02 ng/milliliter (mL) (0.02 micrograms [μg]/L).
  • PSA Response Rate [ Time Frame: Week 3 Day 1 and Week 5 Day 1 ]
    Defined as the proportion of participants with PSA concentration ≥ 50% decrease in PSA from baseline at Week 3 and confirmed at Week 5
  • Time To PSA Progression [ Time Frame: Up to Week 49 Day 1 ]
    Time from baseline to confirmed PSA progression as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines.
  • Testosterone Recovery [ Time Frame: At the 90-day follow-up after 48 weeks of treatment ]
    Cumulative probability of testosterone recovery back to 50 ng/dL or back to baseline or 280 ng/dL at the 90-day follow-up in approximately 150 participants who complete 48 weeks of treatment and who do not plan to start alternative androgen deprivation therapy within the following 12 weeks (or within 24 weeks following the last injection of leuprolide acetate 3-month depot).
  • Absolute Value And Change From Baseline In Quality Of Life (QoL) Total Score As Assessed By The Global Health Domain Of The European Organisation Of Research And Treatment Of Cancer (EORTC)-Quality Of Life Questionnaire (QLQ)-C30 [ Time Frame: Baseline, Week 49 ]
  • Absolute Value And Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30 [ Time Frame: Baseline, Week 49 ]
  • Absolute Value And Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Hormonal-Treatment-Related Symptom Subdomains [ Time Frame: Baseline, Week 49 ]
  • Absolute Value And Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-PR25 [ Time Frame: Baseline, Week 49 ]
  • Absolute Value And Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire [ Time Frame: Baseline, Week 49 ]
  • Incidence Of Treatment-emergent Adverse Events [ Time Frame: Up to 52 weeks ]
    Safety will be evaluated by the incidence and severity of adverse events and the incidence of permanent treatment discontinuation due to adverse events.
  • Serum Concentrations Of Luteinizing Hormone [ Time Frame: Week 1 Day 4, Week 5, Week 25, and Week 49 ]
    Blood samples will be collected from participants for hormonal measurements.
  • Serum Concentrations Of FSH [ Time Frame: Week 1 Day 4, Week 5, Week 25, and Week 49 ]
    Blood samples will be collected from participants for hormonal measurements.
  • Serum Concentrations Of Dihydrotestosterone [ Time Frame: Week 5, Week 25, and Week 49 ]
    Blood samples will be collected from participants for hormonal measurements.
  • Serum Concentrations Of Sex Hormone-Binding Globulin [ Time Frame: Week 5, Week 25, and Week 49 ]
    Blood samples will be collected from participants for hormonal measurements.
  • Maximum Observed Plasma Concentration (Cmax) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose ]
    The Cmax of relugolix will be determined for single and repeat doses in subsets of participants from China or Japan.
  • Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose ]
    The AUC0-τ of relugolix will be determined for single and repeat doses in subsets of participants from China or Japan.
  • Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix [ Time Frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose ]
    The Tmax of relugolix will be determined for single and repeat doses in subsets of participants from China or Japan.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
Castration Rate by Visit [ Time Frame: 1, 2, and3 weeks ]
Castration rate defined as the cumulative probability of testosterone suppression to ≤ 50 ng/dL (1.7 nmol/L) prior to dosing on Week 1 , prior to dosing on Week 2, and prior to dosing on Week 3.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer
Official Title  ICMJE 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
Brief Summary The purpose of this study is to determine the efficacy and safety of relugolix 120 milligrams (mg) orally once daily for 48 weeks on maintaining serum testosterone suppression to castrate levels (< 50 nanograms/deciliter [ng/dL]) in participants with androgen-sensitive advanced prostate cancer.
Detailed Description

This is a phase 3, multinational, randomized, open-label, parallel group study to evaluate the efficacy and safety of oral daily relugolix 120 mg in participants with androgen-sensitive advanced prostate cancer who require at least 1 year of continuous androgen-deprivation therapy. Relugolix 120 mg orally once daily or leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan based on local labels), every 3 months by subcutaneous injection will be administered to participants.

There are 2 analyses for this study, a primary analysis and a final analysis.

Primary Analysis:

The primary analysis of efficacy and safety has been completed (N=934). Participants were randomized 2:1 to receive relugolix or leuprolide for 48 weeks, followed by a 30-day safety follow-up visit or early termination 30-day safety follow-up.

Final Analysis:

The final analysis will occur after additional participants with metastatic disease (approximately 130) have been enrolled and randomized from any sites to the study, and have completed the 48-week treatment period. A cohort of participants being enrolled in China and Taiwan will be analyzed separately once they have completed treatment to support registration in China.

Eligible participants will be randomized 2:1 to relugolix or leuprolide arm 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.

Castration resistance-free survival will be assessed up to Week 49, Day 1 of the study and reported as part of the final analysis.

Approximately 1100 participants will be enrolled in this study, including approximately 130 participants with metastatic advanced prostate cancer to support the analysis of the secondary endpoint of castration resistance-free survival and approximately 130 Chinese participants (enrolled in China and Taiwan) to support registration in China.

Note: To support registration in China, the study will continue to enroll additional nonmetastatic or metastatic participants from China after the final analysis to reach the target enrollment of approximately 130 participants.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Relugolix
    Relugolix 120-mg tablet administered orally once daily following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1
    Other Names:
    • TAK-385
    • MVT-601
    • RVT-601
    • T-1331285
  • Drug: Leuprolide Acetate
    Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection
    Other Name: Leuprolide
Study Arms  ICMJE
  • Experimental: Relugolix
    Relugolix for 48 weeks
    Intervention: Drug: Relugolix
  • Active Comparator: Leuprolide Acetate
    Leuprolide acetate for 48 weeks
    Intervention: Drug: Leuprolide Acetate
Publications * Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. doi: 10.1056/NEJMoa2004325. Epub 2020 May 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 13, 2018)
1100
Original Estimated Enrollment  ICMJE
 (submitted: March 14, 2017)
1125
Estimated Study Completion Date  ICMJE November 1, 2021
Actual Primary Completion Date October 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 1 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.
  3. Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nanomoles [nmol]/liter [L]).
  4. Has a serum PSA concentration at the Screening visit of > 2.0 ng/milliliter (mL) (2.0 microgram [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 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 (for example, taxane-based regimen).
  4. Metastases to brain per prior clinical evaluation.
  5. Participants with myocardial infarction, unstable symptomatic ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months.
  6. Active conduction system abnormalities.
  7. Uncontrolled hypertension.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Trials at Myovant 650-278-8743 ClinicalTrials@Myovant.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Canada,   China,   Denmark,   Finland,   France,   Germany,   Italy,   Japan,   Korea, Republic of,   Netherlands,   New Zealand,   Poland,   Slovakia,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03085095
Other Study ID Numbers  ICMJE MVT-601-3201
2017-000160-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Myovant Sciences GmbH
Study Sponsor  ICMJE Myovant Sciences GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Myovant Medical Monitor Myovant Sciences
PRS Account Myovant Sciences GmbH
Verification Date October 2020

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