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

NCT ID: NCT03085095

Last Updated: 2022-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-18
• Study Completion Date: 2021-11-26

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Relugolix

Relugolix for 48 weeks

Group Type: EXPERIMENTAL

Relugolix

Intervention Type: DRUG

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 Acetate

Leuprolide acetate for 48 weeks

Group Type: ACTIVE_COMPARATOR

Leuprolide Acetate

Intervention Type: DRUG

Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

TAK-385; MVT-601; RVT-601; T-1331285; Leuprolide

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Myovant Sciences GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Myovant Medical Monitor

Role: STUDY_DIRECTOR

Myovant Sciences

Locations

Tucson

Tucson, Arizona, United States

Orange

Orange, California, United States

Denver

Denver, Colorado, United States

Pompano Beach

Pompano Beach, Florida, United States

Jeffersonville

Jeffersonville, Indiana, United States

Des Moines

Des Moines, Iowa, United States

Wichita

Wichita, Kansas, United States

Baltimore

Baltimore, Maryland, United States

Troy

Troy, Michigan, United States

Omaha

Omaha, Nebraska, United States

Las Vegas

Las Vegas, Nevada, United States

Brick

Brick, New Jersey, United States

Albuquerque

Albuquerque, New Mexico, United States

Albany

Albany, New York, United States

Garden City

Garden City, New York, United States

Plainview

Plainview, New York, United States

Poughkeepsie

Poughkeepsie, New York, United States

Syracuse

Syracuse, New York, United States

Durham

Durham, North Carolina, United States

Greensboro

Greensboro, North Carolina, United States

Cincinnati

Cincinnati, Ohio, United States

Middleburg Heights

Middleburg Heights, Ohio, United States

Oklahoma City

Oklahoma City, Oklahoma, United States

Lancaster

Lancaster, Pennsylvania, United States

Myrtle Beach

Myrtle Beach, South Carolina, United States

Nashville

Nashville, Tennessee, United States

San Antonio

San Antonio, Texas, United States

Camperdown

Camperdown, New South Wales, Australia

Tweed Heads

Tweed Heads, New South Wales, Australia

Wahroonga

Wahroonga, New South Wales, Australia

Redcliffe

Redcliffe, Queensland, Australia

Southport

Southport, Queensland, Australia

Linz

Linz, , Austria

Gent

Ghent, Oost-Vlaanderen, Belgium

Brussels

Brussels, , Belgium

Kortrijk

Kortrijk, , Belgium

Itabuna

Itabuna, Estado de Bahia, Brazil

Salvador

Salvador, Estado de Bahia, Brazil

Salvador

Salvador, Estado de Bahia, Brazil

Teresina

Teresina, Piauí, Brazil

Natal

Natal, Rio Grande do Norte, Brazil

Ijuí

Ijuí, Rio Grande do Sul, Brazil

Passo Fundo

Passo Fundo, Rio Grande do Sul, Brazil

Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Joinville

Joinville, Santa Catarina, Brazil

São José Do Rio Preto

São José do Rio Preto, São Paulo, Brazil

Curitiba

Curitiba, , Brazil

Calgary

Calgary, Alberta, Canada

Vancouver

Vancouver, British Columbia, Canada

Halifax

Halifax, Nova Scotia, Canada

Hamilton

Hamilton, Ontario, Canada

London

London, Ontario, Canada

Montreal

Montreal, Quebec, Canada

Sherbrooke

Sherbrooke, Quebec, Canada

Quebec

Québec, , Canada

Nanjing

Nanjing, Jiangsu, China

Changchun

Changchun, Jilin, China

Shanghai

Shanghai, Shanghai Municipality, China

Taiyuan

Taiyuan, Shanxi, China

Beijing

Beijing, , China

Beijing

Beijing, , China

Beijing Shi

Beijing, , China

Chongqing

Chongqing, , China

Hangzhou

Hangzhou, , China

Lanzhou

Lanzhou, , China

Nanchang

Nanchang, , China

Shanghai

Shanghai, , China

Suzhou

Suzhou, , China

Alborg

Aalborg, , Denmark

Aarhus

Aarhus, , Denmark

Herlev

Herlev, , Denmark

Vejle

Vejle, , Denmark

Helsinki

Helsinki, , Finland

Seinajoki

Seinäjoki, , Finland

Tampere

Tampere, , Finland

Turku

Turku, , Finland

Strasbourg

Strasbourg, Bas-Rhin, France

Pierre Benite

Pierre-Bénite, Rhone, France

Creteil

Créteil, Val-de-Marne, France

Lyon

Lyon, , France

Emmendingen

Emmendingen, Baden-Wurttemberg, Germany

Planegg

Planegg, Bavaria, Germany

Braunschweig

Braunschweig, Lower Saxony, Germany

Dresden

Dresden, , Germany

Lubeck

Lübeck, , Germany

Munster

Münster, , Germany

Meldola

Meldola, Emilia-Romagna, Italy

Rome

Rome, Lazio, Italy

Cremona

Cremona, Lombardy, Italy

Candiolo

Candiolo, Piedmont, Italy

Orbassano

Orbassano, Piedmont, Italy

Arezzo

Arezzo, Tuscany, Italy

Milano

Milan, , Italy

Kanazawa-shi

Kanazawa, Ishikawa-ken, Japan

Yokohama

Yokohama, Kanagawa, Japan

Sendai

Sendai, Miyagi, Japan

Sendai

Sendai, Miyagi, Japan

Osaka-sayama

Ōsaka-sayama, Osaka, Japan

Suita

Suita, Osaka, Japan

Bunkyō-Ku

Bunkyō-Ku, Tokyo, Japan

Nakano-ku

Nakano-ku, Tokyo, Japan

Sumida-ku

Sumida-ku, Tokyo, Japan

Chiba

Chiba, , Japan

Fukuoka

Fukuoka, , Japan

Hiroshima

Hiroshima, , Japan

Kita-gun

Kita-ku, , Japan

Kyoto

Kyoto, , Japan

Maebashi

Maebashi, , Japan

Nagasaki

Nagasaki, , Japan

Osaka

Osaka, , Japan

Sapporo

Sapporo, , Japan

Tokyo

Tokyo, , Japan

Ube

Ube, , Japan

Eindhoven

Eindhoven, North Brabant, Netherlands

Amsterdam

Amsterdam, North Holland, Netherlands

Sneek

Sneek, , Netherlands

Christchurch

Christchurch, , New Zealand

Dunedin

Dunedin, , New Zealand

Hamilton

Hamilton, , New Zealand

Tauranga

Tauranga, , New Zealand

Lublin

Lublin, Lublin Voivodeship, Poland

Siedlce

Siedlce, Masovian Voivodeship, Poland

Warszawa

Warsaw, Masovian Voivodeship, Poland

Gdynia

Gdynia, Pomeranian Voivodeship, Poland

Katowice

Katowice, , Poland

Bratislava

Bratislava, , Slovakia

Kosice

Košice, , Slovakia

Kosice

Košice, , Slovakia

Martin

Martin, , Slovakia

Nitra

Nitra, , Slovakia

Poprad

Poprad, , Slovakia

Presov

Prešov, , Slovakia

Sala

Šaľa, , Slovakia

Trencin

Trenčín, , Slovakia

Goyang-Si

Goyang-si, Gyeonggido, South Korea

Busan

Busan, , South Korea

Daegu

Daegu, , South Korea

Hwasun

Hwasun, , South Korea

Seoul

Seoul, , South Korea

Seoul

Seoul, , South Korea

Seoul

Seoul, , South Korea

Seoul

Seoul, , South Korea

A Coruna

A Coruña, A Coruna, Spain

Oviedo

Oviedo, Principality of Asturias, Spain

Barcelona

Barcelona, , Spain

Madrid

Madrid, , Spain

Madrid

Madrid, , Spain

Salamanca

Salamanca, , Spain

Valencia

Valencia, , Spain

Orebro

Örebro, Orebro Ian, Sweden

Stockholm

Stockholm, Sodermandlands Ian, Sweden

Uppsala

Uppsala, Uppsala County, Sweden

Malmo

Malmo, , Sweden

Kaohsiung City

Kaohsiung City, , Taiwan

Taipei

Taipei, , Taiwan

Taipei

Taipei, , Taiwan

Taipei

Taipei, , Taiwan

Exeter

Exeter, Devon, United Kingdom

Scunthorpe

Scunthorpe, North Lincolnshire, United Kingdom

Nottingham

Nottingham, , United Kingdom

Rhyl

Rhyl, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Brazil; Canada; China; Denmark; Finland; France; Germany; Italy; Japan; Netherlands; New Zealand; Poland; Slovakia; South Korea; Spain; Sweden; Taiwan; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 32469183 (View on PubMed)

Shore 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.

Reference Type: DERIVED

PMID: 37713020 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35587650 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000160-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MVT-601-3201

Identifier Type: -

Identifier Source: org_study_id