Clinical trial NCT03085095: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Lead sponsor: Myovant Sciences GmbH
Sponsor class: INDUSTRY
First posted: 2017-03-21
Enrollment: 1134
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 enrolled in China and Taiwan will be analyzed separately once they have completed treatment to support registration in China.

Eligible participants were 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.

The study enrolled 1134 participants, including 139 participants with metastatic advanced prostate cancer to support the analysis of the secondary endpoint of castration resistance-free survival and 93 Chinese participants (enrolled in China and Taiwan) to support registration in China.

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.

Primary outcomes:
measure: Sustained Castration Rate
timeFrame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Secondary outcomes:
measure: Castration Rate At Week 1 Day 4
timeFrame: Week 1 Day 4 (Day 4)
measure: Castration Rate At Week 3 Day 1
timeFrame: Week 3 Day 1 (Day 15)
measure: Confirmed Prostate-specific Antigen (PSA) Response Rate
timeFrame: Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)
measure: Profound Castration Rate At Week 3 Day 1 (Day 15)
timeFrame: Week 3 Day 1 (Day 15)
measure: Follicle-stimulating Hormone (FSH) Level
timeFrame: Week 25 Day 1 (Day 169)
measure: PSA Response Rate At Week 3 Day 1
timeFrame: Week 3 Day 1 (Day 15)
measure: PSA Response Rate At Week 5 Day 1
timeFrame: Week 5 Day 1 (Day 29)
measure: Testosterone Recovery Rate
timeFrame: Day 90 follow-up
measure: Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1
timeFrame: Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)
measure: Profound Castration Rate At Week 1 Day 4 (Day 4)
timeFrame: At Week 1 Day 4 (Day 4)
measure: Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1
timeFrame: Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)
measure: Undetectable PSA Rate
timeFrame: Week 25 Day 1 (Day 169)
measure: Rate Of PSA Progression-free Survival
timeFrame: Week 49 Day 1 (Day 337)
measure: 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
timeFrame: Baseline, Week 49 Day 1 (Day 337)
measure: Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30
timeFrame: Baseline, Week 49 Day 1 (Day 337)
measure: Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains
timeFrame: Baseline, Week 49 Day 1 (Day 337)
measure: Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25
timeFrame: Baseline, Week 49 Day 1 (Day 337)
measure: Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)
timeFrame: Baseline, Week 49 Day 1 (Day 337)
measure: Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone
timeFrame: Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
measure: Percent Change From Baseline In Serum Concentrations Of FSH
timeFrame: Week 1 Day 4 (Day 4), Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
measure: Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone
timeFrame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
measure: Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin
timeFrame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
measure: Maximum Observed Plasma Concentration (Cmax) Of Relugolix
timeFrame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
measure: Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix
timeFrame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
measure: Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix
timeFrame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Other outcomes:
measure: Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE)
timeFrame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Locations:
city: Tucson
country: United States
facility: Tucson
state: Arizona
city: Orange
country: United States
facility: Orange
state: California
city: Denver
country: United States
facility: Denver
state: Colorado
city: Pompano Beach
country: United States
facility: Pompano Beach
state: Florida
city: Jeffersonville
country: United States
facility: Jeffersonville
state: Indiana
city: Des Moines
country: United States
facility: Des Moines
state: Iowa
city: Wichita
country: United States
facility: Wichita
state: Kansas
city: Baltimore
country: United States
facility: Baltimore
state: Maryland
city: Troy
country: United States
facility: Troy
state: Michigan
city: Omaha
country: United States
facility: Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: Las Vegas
state: Nevada
city: Brick
country: United States
facility: Brick
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque
state: New Mexico
city: Albany
country: United States
facility: Albany
state: New York
city: Garden City
country: United States
facility: Garden City
state: New York
city: Plainview
country: United States
facility: Plainview
state: New York
city: Poughkeepsie
country: United States
facility: Poughkeepsie
state: New York
city: Syracuse
country: United States
facility: Syracuse
state: New York
city: Durham
country: United States
facility: Durham
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati
state: Ohio
city: Middleburg Heights
country: United States
facility: Middleburg Heights
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma City
state: Oklahoma
city: Lancaster
country: United States
facility: Lancaster
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Myrtle Beach
state: South Carolina
city: Nashville
country: United States
facility: Nashville
state: Tennessee
city: San Antonio
country: United States
facility: San Antonio
state: Texas
city: Camperdown
country: Australia
facility: Camperdown
state: New South Wales
city: Tweed Heads
country: Australia
facility: Tweed Heads
state: New South Wales
city: Wahroonga
country: Australia
facility: Wahroonga
state: New South Wales
city: Redcliffe
country: Australia
facility: Redcliffe
state: Queensland
city: Southport
country: Australia
facility: Southport
state: Queensland
city: Linz
country: Austria
facility: Linz
city: Gent
country: Belgium
facility: Gent
state: Oost-Vlaanderen
city: Brussels
country: Belgium
facility: Brussels
city: Kortrijk
country: Belgium
facility: Kortrijk
city: Itabuna
country: Brazil
facility: Itabuna
state: Bahia
city: Salvador
country: Brazil
facility: Salvador
state: Bahia
city: Salvador
country: Brazil
facility: Salvador
state: Bahia
city: Teresina
country: Brazil
facility: Teresina
state: Piauí
city: Natal
country: Brazil
facility: Natal
state: Rio Grande Do Norte
city: Ijuí
country: Brazil
facility: Ijuí
state: Rio Grande Do Sul
city: Passo Fundo
country: Brazil
facility: Passo Fundo
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Porto Alegre
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Joinville
state: Santa Catarina
city: São José Do Rio Preto
country: Brazil
facility: São José Do Rio Preto
state: Sao Paulo
city: Curitiba
country: Brazil
facility: Curitiba
city: Calgary
country: Canada
facility: Calgary
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver
state: British Columbia
city: Halifax
country: Canada
facility: Halifax
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton
state: Ontario
city: London
country: Canada
facility: London
state: Ontario
city: Montréal
country: Canada
facility: Montreal
state: Quebec
city: Sherbrooke
country: Canada
facility: Sherbrooke
state: Quebec
city: Quebec
country: Canada
facility: Quebec
city: Nanjing
country: China
facility: Nanjing
state: Jiangsu
city: Chang chun
country: China
facility: Changchun
state: Jilin
city: Shanghai
country: China
facility: Shanghai
state: Shanghai
city: Taiyuan
country: China
facility: Taiyuan
state: Shanxi
city: Beijing
country: China
facility: Beijing
city: Beijing
country: China
facility: Beijing
city: Beijing
country: China
facility: Beijing Shi
city: Chongqing
country: China
facility: Chongqing
city: Hangzhou
country: China
facility: Hangzhou
city: Lanzhou
country: China
facility: Lanzhou
city: Nanchang
country: China
facility: Nanchang
city: Shanghai
country: China
facility: Shanghai
city: Suzhou
country: China
facility: Suzhou
city: Aalborg
country: Denmark
facility: Alborg
city: Aarhus
country: Denmark
facility: Aarhus
city: Herlev
country: Denmark
facility: Herlev
city: Vejle
country: Denmark
facility: Vejle
city: Helsinki
country: Finland
facility: Helsinki
city: Seinäjoki
country: Finland
facility: Seinajoki
city: Tampere
country: Finland
facility: Tampere
city: Turku
country: Finland
facility: Turku
city: Strasbourg
country: France
facility: Strasbourg
state: Bas-Rhin
city: Pierre-Bénite
country: France
facility: Pierre Benite
state: Rhone
city: Créteil
country: France
facility: Creteil
state: Val-de-Marne
city: Lyon
country: France
facility: Lyon
city: Emmendingen
country: Germany
facility: Emmendingen
state: Baden-Wurttemberg
city: Planegg
country: Germany
facility: Planegg
state: Bayern
city: Braunschweig
country: Germany
facility: Braunschweig
state: Niedersachsen
city: Dresden
country: Germany
facility: Dresden
city: Lübeck
country: Germany
facility: Lubeck
city: Münster
country: Germany
facility: Munster
city: Meldola
country: Italy
facility: Meldola
state: Emilia-Romagna
city: Rome
country: Italy
facility: Rome
state: Lazio
city: Cremona
country: Italy
facility: Cremona
state: Lombardia
city: Candiolo
country: Italy
facility: Candiolo
state: Piemonte
city: Orbassano
country: Italy
facility: Orbassano
state: Piemonte
city: Arezzo
country: Italy
facility: Arezzo
state: Toscana
city: Milano
country: Italy
facility: Milano
city: Kanazawa-shi
country: Japan
facility: Kanazawa-shi
state: Isikawa
city: Yokohama
country: Japan
facility: Yokohama
state: Kanagawa
city: Sendai
country: Japan
facility: Sendai
state: Miyagi
city: Sendai
country: Japan
facility: Sendai
state: Miyagi
city: Suita
country: Japan
facility: Suita
state: Osaka
city: Ōsaka-sayama
country: Japan
facility: Osaka-sayama
state: Osaka
city: Bunkyō-Ku
country: Japan
facility: Bunkyō-Ku
state: Tokyo
city: Nakano-ku
country: Japan
facility: Nakano-ku
state: Tokyo
city: Sumida-ku
country: Japan
facility: Sumida-ku
state: Tokyo
city: Chiba
country: Japan
facility: Chiba
city: Fukuoka
country: Japan
facility: Fukuoka
city: Hiroshima
country: Japan
facility: Hiroshima
city: Kita
country: Japan
facility: Kita-gun
city: Kyoto
country: Japan
facility: Kyoto
city: Maebashi
country: Japan
facility: Maebashi
city: Nagasaki
country: Japan
facility: Nagasaki
city: Osaka
country: Japan
facility: Osaka
city: Sapporo
country: Japan
facility: Sapporo
city: Tokyo
country: Japan
facility: Tokyo
city: Ube
country: Japan
facility: Ube
city: Goyang-si
country: Korea, Republic of
facility: Goyang-Si
state: Gyeonggido
city: Busan
country: Korea, Republic of
facility: Busan
city: Daegu
country: Korea, Republic of
facility: Daegu
city: Hwasun
country: Korea, Republic of
facility: Hwasun
city: Seoul
country: Korea, Republic of
facility: Seoul
city: Seoul
country: Korea, Republic of
facility: Seoul
city: Seoul
country: Korea, Republic of
facility: Seoul
city: Seoul
country: Korea, Republic of
facility: Seoul
city: Eindhoven
country: Netherlands
facility: Eindhoven
state: Noord Brabant
city: Amsterdam
country: Netherlands
facility: Amsterdam
state: Noord Holland
city: Sneek
country: Netherlands
facility: Sneek
city: Christchurch
country: New Zealand
facility: Christchurch
city: Dunedin
country: New Zealand
facility: Dunedin
city: Hamilton
country: New Zealand
facility: Hamilton
city: Tauranga
country: New Zealand
facility: Tauranga
city: Lublin
country: Poland
facility: Lublin
state: Lubelskie
city: Siedlce
country: Poland
facility: Siedlce
state: Mazowieckie
city: Warszawa
country: Poland
facility: Warszawa
state: Mazowieckie
city: Gdynia
country: Poland
facility: Gdynia
state: Pomorskie
city: Katowice
country: Poland
facility: Katowice
city: Bratislava
country: Slovakia
facility: Bratislava
city: Košice
country: Slovakia
facility: Kosice
city: Košice
country: Slovakia
facility: Kosice
city: Martin
country: Slovakia
facility: Martin
city: Nitra
country: Slovakia
facility: Nitra
city: Poprad
country: Slovakia
facility: Poprad
city: Prešov
country: Slovakia
facility: Presov
city: Trenčín
country: Slovakia
facility: Trencin
city: Šaľa
country: Slovakia
facility: Sala
city: A Coruña
country: Spain
facility: A Coruna
state: A Coruna
city: Oviedo
country: Spain
facility: Oviedo
state: Asturias
city: Barcelona
country: Spain
facility: Barcelona
city: Madrid
country: Spain
facility: Madrid
city: Madrid
country: Spain
facility: Madrid
city: Salamanca
country: Spain
facility: Salamanca
city: Valencia
country: Spain
facility: Valencia
city: Örebro
country: Sweden
facility: Orebro
state: Orebro Ian
city: Stockholm
country: Sweden
facility: Stockholm
state: Sodermandlands Ian
city: Uppsala
country: Sweden
facility: Uppsala
state: Uppsala Lan
city: Malmö
country: Sweden
facility: Malmo
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung City
city: Taipei
country: Taiwan
facility: Taipei
city: Taipei
country: Taiwan
facility: Taipei
city: Taipei
country: Taiwan
facility: Taipei
city: Exeter
country: United Kingdom
facility: Exeter
state: Devon
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe
state: North Lincolnshire
city: Nottingham
country: United Kingdom
facility: Nottingham
city: Rhyl
country: United Kingdom
facility: Rhyl
Study officials:
affiliation: Myovant Sciences
name: Myovant Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Shore ND, Sutton J. Plain language summary of the HERO study comparing relugolix with leuprolide for men with advanced prostate cancer. Future Oncol. 2022 Jul;18(21):2575-2584. doi: 10.2217/fon-2022-0172. Epub 2022 May 19.