REPLACE-CV: Randomized Study to Evaluate MACE in Patients With Prostate Cancer Treated With Relugolix or Leuprolide Acetate

Sponsor

Myovant Sciences GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05605964

Collaborator

(none)

2,250

Enrollment

Locations

Arms

49.1

Anticipated Duration (Months)

281.3

Patients Per Site

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized study to evaluate the risk of major adverse cardiovascular events (MACE) for relugolix compared with leuprolide acetate. This study will collect clinical and cardiovascular risk factor data on patients ages 18 and older who are receiving relugolix or leuprolide acetate for their prostate cancer or as adjunct to radiation therapy with a treatment plan to be on androgen deprivation therapy (ADT) for at least one year.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Relugolix Drug: Leuprolide Acetate	Phase 3

Detailed Description

Eligible patients will be randomized (1:1) to receive either relugolix or leuprolide acetate for prostate cancer or as an adjunct to primary or salvage radiation therapy. Patients who experience major adverse cardiovascular events (MACE) during the trial will be encouraged to stay on the study and continue to fill out questionnaires every 3 months. Each patient will also be asked to provide information regarding alternative contacts (eg, close relatives or friends, or primary care physician or cardiologist). In addition, patients will provide consent to obtain medical records (eg, hospitalizations, emergency room visits and clinic notes) for additional information, when appropriate.

The primary endpoint in this study will be the time to first adjudicated MACE (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death). A surveillance approach will be used to collect clinical and cardiovascular risk data on patients receiving relugolix or leuprolide acetate for their prostate cancer. A rigorous, blinded adjudication of MACE by an independent clinical event adjudication committee (CEC) is included.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2250 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Relugolix Versus Leuprolide in Patients With Prostate Cancer: A Randomized, Open-Label Study to Assess Major Adverse Cardiovascular Events (REPLACE-CV)

Actual Study Start Date :

Jan 25, 2023

Anticipated Primary Completion Date :

Feb 28, 2027

Anticipated Study Completion Date :

Feb 28, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Relugolix Oral relugolix 120 mg once daily with a loading dose of 360 mg on Day 1	Drug: Relugolix Relugolix tablet Other Names: ORGOVYX TAK-385 MVT-601 RVT-601 T-1331285
Active Comparator: Leuprolide Acetate Subcutaneous or intramuscular leuprolide acetate 22.5 mg 3-M depot or 45 mg 6-M injection	Drug: Leuprolide Acetate Leuprolide acetate injection Other Names: Leuprolide

Arm

Intervention/Treatment

Experimental: Relugolix

Oral relugolix 120 mg once daily with a loading dose of 360 mg on Day 1

Drug: Relugolix

Relugolix tablet

Other Names:

ORGOVYX

TAK-385

MVT-601

RVT-601

T-1331285

Active Comparator: Leuprolide Acetate

Subcutaneous or intramuscular leuprolide acetate 22.5 mg 3-M depot or 45 mg 6-M injection

Drug: Leuprolide Acetate

Leuprolide acetate injection

Other Names:

Leuprolide

Outcome Measures

Primary Outcome Measures

Time to Major Adverse Cardiovascular Event (MACE) [From date of enrollment until date of first confirmed MACE, assessed up to 5 years]
Time to first adjudicated MACE defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death

Secondary Outcome Measures

Time Course of Events Related to MACE [From date of enrollment until date of first confirmed MACE, assessed up to 5 years]
Time to first adjudicated MACE or death due to all cause, time to first adjudicated nonfatal or fatal myocardial infarction, time to first adjudicated nonfatal or fatal stroke, time to adjudicated cardiovascular death, time to recurrent adjudicated MACE, and time to start of ADT in combination with enzalutamide/abiraterone/apalutamide/darolutamide for disease progression
Incidence of Safety Outcomes [Screening; Day 1; 3, 6, 9, and 12 months; and every 3 months thereafter]
Incidence of selective safety data including all treatment-emergent serious adverse events, nonserious adverse events leading to discontinuation of relugolix or leuprolide acetate, and clinical laboratory tests as obtained per standard of care

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Has voluntarily signed and dated the informed consent form prior to baseline visit;
Is a male and 18 years of age or older on the day of signing and dating the informed consent form;
Patient has sufficient cognitive function in the investigator's opinion to complete the questionnaires and other activities related to the study;
Has a histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate;
Is, in the opinion of the investigator, a candidate for at least 1 year of continuous ADT for the management of prostate cancer with one of the following clinical disease state presentations:
Evidence of biochemical (prostate-specific antigen [PSA], confirmed with two measurements at least one week apart) 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);
Newly diagnosed hormone-sensitive metastatic disease (metastases in regional lymph node[s] are considered N1 and will, therefore, be stratified as non-metastatic);
Advanced localized disease unlikely to be cured by local primary intervention with curative intent;
Patients receiving primary or salvage radiation therapy with adjuvant ADT;
Patients with high-risk cardiovascular disease defined as prior history of MACE (myocardial infarction, stroke, coronary revascularization [including percutaneous procedures] or revascularization affecting cerebral blood flow [including carotid procedures]) > 1 month before enrollment in the study; OR
Patients with ≥ 3 of the following cardiovascular risk factors:
Age (≥ 55 years of age);
Hypertension defined as self-reported high blood pressure, or use of a blood pressure-lowering medication;
Diabetes defined as self-reported diabetes or use of hypoglycemic medication;
Dyslipidemia defined as self-reported high cholesterol or use of a lipid-lowering medication;
Current cigarette use, defined as smoking within the year prior to the screening visit;
Family history of cardiovascular disease, defined as a myocardial infarction or stroke or coronary revascularization or revascularization affecting cerebral blood flow (ie, carotid procedures) or sudden death in a first-degree relative < 60 years old;
Serum testosterone before starting relugolix or leuprolide acetate of ≥ 150 ng/dL (1.50 ng/mL or 5.2 nmol/L) within 6 months prior to screening;
Serum PSA concentration of > 2.0 ng/mL (2.0 μg/L) or, when applicable, post radical prostatectomy of > 0.2 ng/mL (0.2 μg/L) within 6 months prior to screening (by medical history);
Patients, in the opinion of the investigator, must be equally eligible for either treatment in the study. If either the patient or the physician has a strong preference that one of the treatments be prescribed over the other, the patient must not be enrolled;
Patients must not be participating or intending to participate in an interventional therapeutic study.

Exclusion Criteria:

Any significant cardiovascular conditions per the investigator within 1 month before study entry including but not limited to: myocardial infarction, stroke, New York Heart Association class III or IV heart failure, thromboembolic events, major cardiovascular or cerebrovascular procedures or any other condition that in the investigator's opinion puts the patient at unacceptable risk to enter the study;
Any major cardiovascular or cerebrovascular procedures planned within the 1 month after enrollment;
Patients with QT interval corrected for heart rate (QTc) determined using Fridericia's formula (QTcF; QTcF = QT/[R-R interval ^0.33]) > 470 msec within 6 months of screening;
Uncontrolled hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg) at the time of screening;
Previously received gonadotropin-releasing hormone (GnRH) receptor agonist (eg, leuprolide, goserelin, histrelin, triptorelin), GnRH receptor antagonist, or other forms of ADT (estrogen or antiandrogen) for > 18 months total duration. If ADT was received for ≤ 18 months total duration, then that therapy must have been completed at least 12 months prior to baseline. Once enrolled in the study, patients may be treated with ADT and anti-androgen (abiraterone, enzalutamide, apalutamide, darolutamide);
Metastases to brain per prior clinical evaluation;
Prescriber plans to switch from relugolix to leuprolide acetate or another GnRH agonist or antagonist or from leuprolide acetate to relugolix or another GnRH agonist or antagonist during the study;
Treatment with any investigational product within 28 days or 5 half-lives (whichever is longer). Exception: treatment for prostate cancer with any investigational products where the mechanism of action is testosterone lowering. In this circumstance, there must be a minimum 12-month treatment free interval;
Active malignancy beyond prostate cancer with the exception of the following:
Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin;
Adequately treated Stage I cancer from which the patient is currently disease-free for ≥ 2 years;
Any other cancer from which the patient has been disease-free for ≥ 5 years;
Other malignancy upon agreement with the medical monitor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Urology Specialists, PLLC	Tucson	Arizona	United States	85704
2	Florida Urology Partners, LLP	Tampa	Florida	United States	33578
3	Florida Urology Partners, LLP	Tampa	Florida	United States	33609
4	Northwestern University	Chicago	Illinois	United States	60611
5	Houston Metro Urology CRC, LLC	Houston	Texas	United States	77027
6	Potomac Urology Center, PC	Alexandria	Virginia	United States	22311
7	Urology of Virginia	Virginia Beach	Virginia	United States	23462
8	Potomac Urology	Woodbridge	Virginia	United States	22191