Prostate CancerPhase 3HERONCT03085095
A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer
A Phase 3 study testing Relugolix and Leuprolide Acetate in people with Prostate Cancer, run by Myovant Sciences GmbH at 162 sites in 22 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Relugolix and Leuprolide Acetate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,134 participants
- Where
- 162 sitesin 22 countries
- Study dates
- 18 Apr 2017to 26 Nov 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
- 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:
- 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
- Newly diagnosed androgen-sensitive metastatic disease; or
- Advanced localized disease unlikely to be cured by local primary intervention with either surgery or radiation with curative intent.
- Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nanomoles [nmol]/liter [L]).
- 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.
- Has an Eastern Cooperative Oncology Group performance status of 0 or 1 at initial screening and at baseline.
Who cannot join
- 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.
- 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.
- Previous systemic cytotoxic treatment for prostate cancer (for example, taxane-based regimen).
- Metastases to brain per prior clinical evaluation.
- Participants with myocardial infarction, unstable symptomatic ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months.
- Active conduction system abnormalities.
- Uncontrolled hypertension.
Trial locations and contacts
162 sites in 22 countries.
162 sites in 22 countries
United States27 sites
Albany
Albany, New York, 12208
Albuquerque
Albuquerque, New Mexico, 87109
Baltimore
Baltimore, Maryland, 21204
Brick
Brick, New Jersey, 08724
Cincinnati
Cincinnati, Ohio, 45212
Denver
Denver, Colorado, 80211
Des Moines
Des Moines, Iowa, 50266
Durham
Durham, North Carolina, 27710
Garden City
Garden City, New York, 11530
Greensboro
Greensboro, North Carolina, 27403
Jeffersonville
Jeffersonville, Indiana, 47130
Lancaster
Lancaster, Pennsylvania, 17604
Las Vegas
Las Vegas, Nevada, 89135
Middleburg Heights
Middleburg Heights, Ohio, 44130
Myrtle Beach
Myrtle Beach, South Carolina, 29572
Nashville
Nashville, Tennessee, 37209
Oklahoma City
Oklahoma City, Oklahoma, 73104
Omaha
Omaha, Nebraska, 68130
Orange
Orange, California, 92868
Plainview
Plainview, New York, 11803
Pompano Beach
Pompano Beach, Florida, 33060
Poughkeepsie
Poughkeepsie, New York, 12601
San Antonio
San Antonio, Texas, 78258
Syracuse
Syracuse, New York, 13210
Troy
Troy, Michigan, 48084
Tucson
Tucson, Arizona, 85741
Wichita
Wichita, Kansas, 67226
Japan20 sites
Bunkyō-Ku
Bunkyō-Ku, Tokyo, 113-8655
Chiba
Chiba, 260-0801
Fukuoka
Fukuoka, 812-0033
Hiroshima
Hiroshima, 730-8518
Kanazawa-shi
Kanazawa, Ishikawa-ken, 920-8641
Kita-gun
Kita-ku, 761-0793
Kyoto
Kyoto, 606-8507
Maebashi
Maebashi, 371-8511
Nagasaki
Nagasaki, 852-8501
Nakano-ku
Nakano-ku, Tokyo, 164-8541
Osaka
Osaka, 541-8567
Osaka-sayama
Ōsaka-sayama, Osaka, 589-8511
Sapporo
Sapporo, 003-0804
Sendai
Sendai, Miyagi, 9808574
Sendai
Sendai, Miyagi, 9818563
Suita
Suita, Osaka, 565-0871
Sumida-ku
Sumida-ku, Tokyo, 130-8587
Tokyo
Tokyo, 285-8741
Ube
Ube, 7558505
Yokohama
Yokohama, Kanagawa, 232-0024
China13 sites
Beijing
Beijing, 100041
Beijing
Beijing, 100050
Beijing Shi
Beijing, 100730
Changchun
Changchun, Jilin, 130021
Chongqing
Chongqing, 400030
Hangzhou
Hangzhou, 310003
Lanzhou
Lanzhou, 730030
Nanchang
Nanchang, 330006
Nanjing
Nanjing, Jiangsu, 210008
Shanghai
Shanghai, Shanghai Municipality, 020043
Shanghai
Shanghai, 200040
Suzhou
Suzhou, 215004
Taiyuan
Taiyuan, Shanxi, 030001
Brazil12 sites
Curitiba
Curitiba, 81520-060
Ijuí
Ijuí, Rio Grande do Sul, 98700
Itabuna
Itabuna, Estado de Bahia, 45602-650
Joinville
Joinville, Santa Catarina, 89201-260
Natal
Natal, Rio Grande do Norte, 59062-000
Passo Fundo
Passo Fundo, Rio Grande do Sul, 99010-080
Porto Alegre
Porto Alegre, Rio Grande do Sul, 90110-270
Porto Alegre
Porto Alegre, Rio Grande do Sul, 90430-090
Salvador
Salvador, Estado de Bahia, 41253-190
Salvador
Salvador, Estado de Bahia, 41820-021
São José Do Rio Preto
São José do Rio Preto, São Paulo, 15090-000
Teresina
Teresina, Piauí, 64001-280
Slovakia9 sites
Bratislava
Bratislava, 851 05
Kosice
Košice, 040 01
Kosice
Košice, 041 91
Martin
Martin, 036 59
Nitra
Nitra, 949 01
Poprad
Poprad, 058 45
Presov
Prešov, 080 01
Sala
Šaľa, 927 01
Trencin
Trenčín, 911 01
Canada8 sites
Calgary
Calgary, Alberta, T2V4R6
Halifax
Halifax, Nova Scotia, B3H2Y9
Hamilton
Hamilton, Ontario, L8N4A6
London
London, Ontario, N6A4G5
Montreal
Montreal, Quebec, H2X0A9
Quebec
Québec, G1R 3S3
Sherbrooke
Sherbrooke, Quebec, J1H5N4
Vancouver
Vancouver, British Columbia, V5Z1M9
South Korea8 sites
Busan
Busan, 49241
Daegu
Daegu, 41404
Goyang-Si
Goyang-si, Gyeonggido, 10408
Hwasun
Hwasun, 58128
Seoul
Seoul, 03080
Seoul
Seoul, 05505
Seoul
Seoul, 06273
Seoul
Seoul, 06351
Italy7 sites
Arezzo
Arezzo, Tuscany, 52100
Candiolo
Candiolo, Piedmont, 10060
Cremona
Cremona, Lombardy, 26100
Meldola
Meldola, Emilia-Romagna, 47014
Milano
Milan, 20162
Orbassano
Orbassano, Piedmont, 10043
Rome
Rome, Lazio, 00152
Spain7 sites
A Coruna
A Coruña, A Coruna, 15706
Barcelona
Barcelona, 08036
Madrid
Madrid, 28007
Madrid
Madrid, 28041
Oviedo
Oviedo, Principality of Asturias, 33011
Salamanca
Salamanca, 37007
Valencia
Valencia, 46009
Germany6 sites
Braunschweig
Braunschweig, Lower Saxony, 38100
Dresden
Dresden, 01307
Emmendingen
Emmendingen, Baden-Wurttemberg, 79312
Lubeck
Lübeck, 23538
Munster
Münster, 48149
Planegg
Planegg, Bavaria, 82152
Australia5 sites
Camperdown
Camperdown, New South Wales, 2050
Redcliffe
Redcliffe, Queensland, 4020
Southport
Southport, Queensland, 4215
Tweed Heads
Tweed Heads, New South Wales, 2485
Wahroonga
Wahroonga, New South Wales, 2076
Poland5 sites
Gdynia
Gdynia, Pomeranian Voivodeship, 81-519
Katowice
Katowice, 40611
Lublin
Lublin, Lublin Voivodeship, 20-582
Siedlce
Siedlce, Masovian Voivodeship, 08-110
Warszawa
Warsaw, Masovian Voivodeship, 02-797
Denmark4 sites
Alborg
Aalborg, DK-9000
Aarhus
Aarhus, 8200
Herlev
Herlev, 2730
Vejle
Vejle, DK-7100
Finland4 sites
Helsinki
Helsinki, FI-00029
Seinajoki
Seinäjoki, FI-60220
Tampere
Tampere, FI-33520
Turku
Turku, FI-20520
France4 sites
Creteil
Créteil, Val-de-Marne, 94010
Lyon
Lyon, 69437
Pierre Benite
Pierre-Bénite, Rhone, 69495
Strasbourg
Strasbourg, Bas-Rhin, 67091
New Zealand4 sites
Christchurch
Christchurch, 8013
Dunedin
Dunedin, 9016
Hamilton
Hamilton, 3204
Tauranga
Tauranga, 3112
Sweden4 sites
Malmo
Malmö, SE-20502
Orebro
Örebro, Orebro Ian, SE-70185
Stockholm
Stockholm, Sodermandlands Ian, SE-17176
Uppsala
Uppsala, Uppsala County, SE-751-85
Taiwan4 sites
Kaohsiung City
Kaohsiung City, 807
Taipei
Taipei, 100
Taipei
Taipei, 111
Taipei
Taipei, 11490
United Kingdom4 sites
Exeter
Exeter, Devon, EX2 5DW
Nottingham
Nottingham, NG5 1PB
Rhyl
Rhyl, LL18 5UJ
Scunthorpe
Scunthorpe, North Lincolnshire, DN157BH
Belgium3 sites
Brussels
Brussels, 1200
Gent
Ghent, Oost-Vlaanderen, 9000
Kortrijk
Kortrijk, 8500
Netherlands3 sites
Amsterdam
Amsterdam, North Holland, 1105AZ
Eindhoven
Eindhoven, North Brabant, 5623EJ
Sneek
Sneek, 8601 ZK
About this study
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
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.
Read the 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.
- Conditions
- Prostate Cancer
- Being tested
- Relugolix, Leuprolide Acetate
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RelugolixDrug
Also called TAK-385, MVT-601, RVT-601, T-1331285
Relugolix 120-mg tablet administered orally once daily following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1
Leuprolide AcetateDrug
Also called Leuprolide
Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Relugolix | Experimental | Relugolix for 48 weeks Receives: Drug: Relugolix |
| Leuprolide Acetate | Active comparator | Leuprolide acetate for 48 weeks Receives: Drug: Leuprolide Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sustained Castration Rate
Sustained castration rate defined as the cumulative probability of testosterone suppression to < 50 nanogram (ng)/deciliter (dL). The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
The lower bound of the 95% confidence interval (CI) for the cumulative probability of sustained testosterone suppression in the relugolix treatment group must have been ≥ 90% to meet evaluation criteria for efficacy.
Measured: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Secondary outcomes (25)
Castration Rate At Week 1 Day 4
Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 1 Day 4 (Day 4)
Castration Rate At Week 3 Day 1
Castration rate was defined as the cumulative probability of testosterone suppression to < 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 3 Day 1 (Day 15)
Confirmed Prostate-specific Antigen (PSA) Response Rate
Confirmed PSA response defined as > 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.
Measured: Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)
Profound Castration Rate At Week 3 Day 1 (Day 15)
Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 3 Day 1 (Day 15)
Follicle-stimulating Hormone (FSH) Level
To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.
Measured: Week 25 Day 1 (Day 169)
PSA Response Rate At Week 3 Day 1
PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 3 Day 1 (Day 15)
PSA Response Rate At Week 5 Day 1
PSA response defined as > 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 5 Day 1 (Day 29)
Testosterone Recovery Rate
The cumulative probability of testosterone recovery back to > 280 ng/dL (lower limit of the normal range), back to ≥ 50 ng/dL (definition of castration), and back to > 280 ng/dL or baseline at 90 days after drug discontinuation was assessed. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Measured: Day 90 follow-up
Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1
Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)
Profound Castration Rate At Week 1 Day 4 (Day 4)
Castration rate defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.
Measured: At Week 1 Day 4 (Day 4)
Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1
Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to < 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)
Undetectable PSA Rate
Defined as the proportion of participants with PSA concentration < 0.02 ng/milliliter (mL).The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 25 Day 1 (Day 169)
Rate Of PSA Progression-free Survival
PSA progression was defined as the first increase in PSA of 25% or greater and 2 ng/mL or greater above the nadir with confirmation by a second consecutive PSA measurement at least 3 weeks later. For participants without declining PSA from baseline, a PSA increase of ≥ 25% and ≥ 2 ng/mL from baseline beyond 12 weeks was considered PSA progression. The rate of progression-free survival was estimated using the Kaplan-Meier method and reported as percentage of participants.
Measured: Week 49 Day 1 (Day 337)
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
The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. The global health and quality of life domain is presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Measured: Baseline, Week 49 Day 1 (Day 337)
Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30
The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. All domains except for the global health and quality are presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Measured: Baseline, Week 49 Day 1 (Day 337)
Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains
Subscales for assessment of hormonal treatment-related symptoms (6 items) and sexual activity and function (6 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Measured: Baseline, Week 49 Day 1 (Day 337)
Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25
Subscale assessments of urinary symptoms (9 items) and bowel symptoms (4 items) from the EORTC-QLQ-PR25 25-item prostate cancer module of the EORTC are presented. Questions used 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale. A decrease in symptom scores indicates improvement (lower level of symptoms/problems).
Measured: Baseline, Week 49 Day 1 (Day 337)
Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)
The EuroQoL EQ-5D-5L comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 levels: no problems (1 as numerical score), slight problems (2 as numerical score), moderate problems (3 as numerical score), severe problems (4 as numerical score), and extreme problems (5 as numerical score). The total score ranges from 0 to 100. A decrease in score indicates improvement.
Measured: Baseline, Week 49 Day 1 (Day 337)
Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone
Blood samples were collected from participants for hormonal measurements.
Measured: 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)
Percent Change From Baseline In Serum Concentrations Of FSH
Blood samples were collected from participants for hormonal measurements.
Measured: 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)
Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone
Blood samples were collected from participants for hormonal measurements.
Measured: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin
Blood samples were collected from participants for hormonal measurements.
Measured: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Maximum Observed Plasma Concentration (Cmax) Of Relugolix
The Cmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose pharmacokinetics (PK) was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix
The AUC0-τ of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix
The Tmax of relugolix was determined for single and repeat doses in subsets of participants from Japan. Single dose PK was assessed on Day 1 following an initial 360 mg dose of relugolix. Repeat dose PK was assessed following repeat dosing of relugolix 120 mg once daily for 2 weeks.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2017
- Study start18 Apr 2017
- Primary completion25 Oct 2019
- Study completion26 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Myovant Sciences GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Myovant Medical Monitor, Study director, Myovant Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03085095
- Sponsor's protocol ID
- MVT-601-3201
- Other IDs
- 2017-000160-15, 2017
- Acronym
- HERO
- Status last verified
- Jan 2022
- First submitted
- 9 Mar 2017
- Last updated
- 18 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32469183Shore ND, Mehlhaff BA, Cookson MS, Saltzstein DR, Tutrone R, Brown B, Lu S, Fallick M, Hanson S, Saad F. Impact of Concomitant Cardiovascular Therapies on Efficacy and Safety of Relugolix vs Leuprolide: Subgroup Analysis from HERO Study in Advanced Prostate Cancer. Adv Ther. 2023 Nov;40(11):4919-4927. doi: 10.1007/s12325-023-02634-7. Epub 2023 Sep 15.
PubMed 37713020Shore 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.
PubMed 35587650
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03085095
- Acronym / sponsor ID
- HERO / MVT-601-3201
- Conditions
- Prostate Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,134 participants (actual)
- Lead sponsor
- Myovant Sciences GmbHIndustry (pharma, biotech, devices)
- Study start
- 18 Apr 2017 (actual)
- Primary completion
- 25 Oct 2019 (actual)
- Study completion
- 26 Nov 2021 (actual)
- First posted
- 21 Mar 2017 (actual)
- Results
- Posted 25 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Relugolix | Experimental | Drug: RelugolixRelugolix for 48 weeks |
| Leuprolide Acetate | Active comparator | Drug: Leuprolide AcetateLeuprolide acetate for 48 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
- 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:
- Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nanomoles [nmol]/liter [L]).
- 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.
- Has an Eastern Cooperative Oncology Group performance status of 0 or 1 at initial screening and at baseline.
Key exclusion criteria (7 listed)
- 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.
- 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.
- Previous systemic cytotoxic treatment for prostate cancer (for example, taxane-based regimen).
- Metastases to brain per prior clinical evaluation.
- Participants with myocardial infarction, unstable symptomatic ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RelugolixAlso: TAK-385, MVT-601, RVT-601, T-1331285Relugolix 120-mg tablet administered orally once daily following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1 | Drug | Relugolix |
| Leuprolide AcetateAlso: LeuprolideLeuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection | Drug | Leuprolide Acetate |
Primary outcome
Sustained Castration Rate
Time frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
Sustained castration rate defined as the cumulative probability of testosterone suppression to < 50 nanogram (ng)/deciliter (dL). The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants. The lower bound of the 95% confidence interval (CI) for the cumulative probability of sustained testosterone suppression in the relugolix treatment group must have been ≥ 90% to meet evaluation criteria for efficacy.
25 secondary outcomes
Castration Rate At Week 1 Day 4
Time frame: Week 1 Day 4 (Day 4)
Castration Rate At Week 3 Day 1
Time frame: Week 3 Day 1 (Day 15)
Confirmed Prostate-specific Antigen (PSA) Response Rate
Time frame: Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)
Profound Castration Rate At Week 3 Day 1 (Day 15)
Time frame: Week 3 Day 1 (Day 15)
Follicle-stimulating Hormone (FSH) Level
Time frame: Week 25 Day 1 (Day 169)
PSA Response Rate At Week 3 Day 1
Time frame: Week 3 Day 1 (Day 15)
PSA Response Rate At Week 5 Day 1
Time frame: Week 5 Day 1 (Day 29)
Testosterone Recovery Rate
Time frame: Day 90 follow-up
Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1
Time frame: Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)
Profound Castration Rate At Week 1 Day 4 (Day 4)
Time frame: At Week 1 Day 4 (Day 4)
Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1
Time frame: Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)
Undetectable PSA Rate
Time frame: Week 25 Day 1 (Day 169)
Rate Of PSA Progression-free Survival
Time frame: Week 49 Day 1 (Day 337)
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 Day 1 (Day 337)
Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30
Time frame: Baseline, Week 49 Day 1 (Day 337)
Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains
Time frame: Baseline, Week 49 Day 1 (Day 337)
Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25
Time frame: Baseline, Week 49 Day 1 (Day 337)
Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)
Time frame: Baseline, Week 49 Day 1 (Day 337)
Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone
Time frame: 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)
Percent Change From Baseline In Serum Concentrations Of FSH
Time frame: 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)
Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone
Time frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin
Time frame: Week 5 Day 1 (Day 29), Week 25 Day 1 (Day 169), and Week 49 Day 1 (Day 337)
Maximum Observed Plasma Concentration (Cmax) Of Relugolix
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours postdose on Day 1 and Week 2
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 on Day 1 and Week 2
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 on Day 1 and Week 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32469183Shore 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.
- Derived from this study: PubMed 37713020Shore ND, Mehlhaff BA, Cookson MS, Saltzstein DR, Tutrone R, Brown B, Lu S, Fallick M, Hanson S, Saad F. Impact of Concomitant Cardiovascular Therapies on Efficacy and Safety of Relugolix vs Leuprolide: Subgroup Analysis from HERO Study in Advanced Prostate Cancer. Adv Ther. 2023 Nov;40(11):4919-4927. doi: 10.1007/s12325-023-02634-7. Epub 2023 Sep 15.
- Derived from this study: PubMed 35587650Shore 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Myovant Medical Monitor study director
Myovant Sciences
162 sites in 22 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Relugolix and Leuprolide Acetate in people with Prostate Cancer, run by Myovant Sciences GmbH at 162 sites in 22 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 162 sites in United States, Japan, China, Brazil, Slovakia and 17 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sustained Castration Rate (time frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03085095, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2022.