TriangleNCT03085095 · CITED IN SOURCE DOCUMENTS
A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2022-01-18
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Sustained Castration Rate
Castration Rate At Week 1 Day 4
Castration Rate At Week 3 Day 1
Confirmed Prostate-specific Antigen (PSA) Response Rate
Profound Castration Rate At Week 3 Day 1 (Day 15)
Follicle-stimulating Hormone (FSH) Level
PSA Response Rate At Week 3 Day 1
PSA Response Rate At Week 5 Day 1
Testosterone Recovery Rate
Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1
Profound Castration Rate At Week 1 Day 4 (Day 4)
Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1
Undetectable PSA Rate
Rate Of PSA Progression-free Survival
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
Change From Baseline In QoL Total Score For Remaining Domain Scores As Assessed By The EORTC-QLQ-C30
Change From Baseline In QoL Total Score As Assessed By The EORTC-QLQ-PR25 Sexual Activity And Functioning And Hormonal-Treatment-Related Symptom Subdomains
Change From Baseline In QoL Total Score For Urinary And Bowel Symptoms Domains As Assessed By The EORTC-QLQ-PR25
Change From Baseline In QoL Total Score As Assessed By The European Quality Of Life 5-Dimension 5-Level Questionnaire (EuroQoL EQ-5D-5L)
Percent Change From Baseline In Serum Concentrations Of Luteinizing Hormone
Percent Change From Baseline In Serum Concentrations Of FSH
Percent Change From Baseline In Serum Concentrations Of Dihydrotestosterone
Percent Change From Baseline In Serum Concentrations Of Sex Hormone-Binding Globulin
Maximum Observed Plasma Concentration (Cmax) Of Relugolix
Area Under The Concentration-Time Curve (AUC0-τ) Of Relugolix
Time To Maximum Observed Plasma Concentration (Tmax) Of Relugolix
Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- MALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Relugolix for 48 weeks
- intervention Names
- Drug: Relugolix
- label
- Relugolix
- type
- EXPERIMENTAL
- description
- Leuprolide acetate for 48 weeks
- intervention Names
- Drug: Leuprolide Acetate
- label
- Leuprolide Acetate
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Relugolix
- description
- Relugolix 120-mg tablet administered orally once daily following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1
- name
- Relugolix
- other Names
- TAK-385
- MVT-601
- RVT-601
- T-1331285
- type
- DRUG
- arm Group Labels
- Leuprolide Acetate
- description
- Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection
- name
- Leuprolide Acetate
- other Names
- Leuprolide
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 1134
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- description
- MACE were defined as nonfatal myocardial infarction, nonfatal stroke, and death from any cause.
- measure
- Percentage of Participants Who Experienced Major Adverse Cardiovascular Events (MACE)
- time Frame
- From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
- primary Outcomes
- description
- 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.
- measure
- Sustained Castration Rate
- time Frame
- From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)
- secondary Outcomes
- description
- 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.
- measure
- Castration Rate At Week 1 Day 4
- time Frame
- Week 1 Day 4 (Day 4)
- description
- 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.
- measure
- Castration Rate At Week 3 Day 1
- time Frame
- Week 3 Day 1 (Day 15)
- description
- Confirmed PSA response defined as \> 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.
- measure
- Confirmed Prostate-specific Antigen (PSA) Response Rate
- time Frame
- Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)
- description
- 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.
- measure
- Profound Castration Rate At Week 3 Day 1 (Day 15)
- time Frame
- Week 3 Day 1 (Day 15)
- description
- To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.
- measure
- Follicle-stimulating Hormone (FSH) Level
- time Frame
- Week 25 Day 1 (Day 169)
- description
- 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.
- measure
- PSA Response Rate At Week 3 Day 1
- time Frame
- Week 3 Day 1 (Day 15)
- description
- 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.
- measure
- PSA Response Rate At Week 5 Day 1
- time Frame
- Week 5 Day 1 (Day 29)
- description
- 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.
- measure
- Testosterone Recovery Rate
- time Frame
- Day 90 follow-up
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- Profound Castration Rate At Week 1 Day 4 (Day 4)
- time Frame
- At Week 1 Day 4 (Day 4)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- Undetectable PSA Rate
- time Frame
- Week 25 Day 1 (Day 169)
Full study description
- 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.
Source references
- 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.
- pmid
- 32469183
- type
- BACKGROUND
- citation
- 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.
- pmid
- 37713020
- type
- DERIVED
- 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.
- pmid
- 35587650
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice