Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03085095
Recruitment Status : Recruiting
First Posted : March 21, 2017
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Myovant Sciences GmbH

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]; 1.7 nanomoles/liter [nmol/L]) in participants with androgen-sensitive advanced prostate cancer.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Relugolix Drug: Leuprolide Acetate Phase 3

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.

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 castration resistance free survival and 138 Chinese participants (enrolled in China and Taiwan) to support registration in China.

There are 2 analyses for this study, a primary analysis and a final analysis. The primary analysis of efficacy and safety will occur after approximately 915 participants have been randomized to the study and evaluated for 48 weeks and completed the 30-day safety follow-up visit or discontinued early with 30-day safety follow-up. The final analysis will occur after approximately 390 participants with metastatic disease (or approximately 1100 participants with or without metastatic prostate cancer) have been randomized from any sites to the study. 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 138 participants.

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 18, 2017
Actual Primary Completion Date : October 25, 2019
Estimated Study Completion Date : November 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Relugolix
Relugolix for 48 weeks
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

Active Comparator: Leuprolide Acetate
Leuprolide acetate for 48 weeks
Drug: Leuprolide Acetate
Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan), every 3 months by subcutaneous injection
Other Name: Leuprolide




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. Follicle-Stimulating Hormone (FSH) Level [ Time Frame: Week 25 Day 1 ]
    To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.

  5. 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.

  6. 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.

  7. 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.

  8. 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).

  9. 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).

  10. 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

  11. 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.

  12. 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).

  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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.

  19. 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.

  20. 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.

  21. Serum Concentrations Of Dihydrotestosterone [ Time Frame: Week 5, Week 25, and Week 49 ]
    Blood samples will be collected from participants for hormonal measurements.

  22. 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.

  23. 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.

  24. 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.

  25. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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 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 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03085095


Contacts
Layout table for location contacts
Contact: Clinical Trials at Myovant 650-278-8743 ClinicalTrials@Myovant.com

Locations
Show Show 208 study locations
Sponsors and Collaborators
Myovant Sciences GmbH
Investigators
Layout table for investigator information
Study Director: Myovant Medical Monitor Myovant Sciences
Publications:
Layout table for additonal information
Responsible Party: Myovant Sciences GmbH
ClinicalTrials.gov Identifier: NCT03085095    
Other Study ID Numbers: MVT-601-3201
2017-000160-15 ( EudraCT Number )
First Posted: March 21, 2017    Key Record Dates
Last Update Posted: August 11, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Leuprolide
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents