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

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

Tracking Information

• First Submitted Date: March 9, 2017
• First Posted Date: March 21, 2017
• Last Update Posted Date: October 29, 2020
• Actual Study Start Date: April 18, 2017
• Actual Primary Completion Date: October 25, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: 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
• 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• 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

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 13, 2018): 1100
• Original Estimated Enrollment (submitted: March 14, 2017): 1125
• Estimated Study Completion Date: November 1, 2021
• Actual Primary Completion Date: October 25, 2019 (Final data collection date for primary outcome measure)

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 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

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials at Myovant; 650-278-8743; ClinicalTrials@Myovant.com

• Listed Location Countries: 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

Administrative Information

• NCT Number: NCT03085095
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Myovant Sciences GmbH
• Study Sponsor: Myovant Sciences GmbH
• Collaborators: Not Provided

Investigators

• Study Director: Myovant Medical Monitor; Myovant Sciences

• PRS Account: Myovant Sciences GmbH
• Verification Date: October 2020