Study of Relugolix in Men With Metastatic Castration-Sensitive Prostate Cancer or Non-Metastatic or Metastatic Castration-Resistant Prostate Cancer

Sponsor

Myovant Sciences GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04666129

Collaborator

(none)

Enrollment

Locations

Arms

32.4

Anticipated Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is being conducted to assess the safety and tolerability of relugolix with other agents approved for use in combination with androgen deprivation therapy (ADT) for a 12-week treatment period and an additional 40-week safety extension period in men with prostate cancer, either metastatic castration-sensitive prostate cancer (mCSPC) or non-metastatic or metastatic castration-resistant prostate cancer (nmCRPC or mCRPC).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castration-Resistant Prostate Cancer Metastatic Castration-Sensitive Prostate Cancer Non-Metastatic Castration-Resistant Prostate Cancer	Drug: Relugolix Drug: Abiraterone Drug: Prednisone Drug: Methylprednisolone Drug: Apalutamide Drug: Docetaxel	Phase 1

Detailed Description

This is a three-part, open-label, parallel-cohort study to assess the safety and tolerability of relugolix as the ADT component in combination treatment with abiraterone acetate plus a corticosteroid in patients with mCSPC or mCRPC (Part 1), apalutamide in patients with mCSPC or nmCRPC (Part 2), or docetaxel with or without prednisone in patients with mCSPC or mCRPC (Part 3).

The study will consist of a 45-day screening period followed by a 12-week treatment period with one of the three combination treatments (Parts 1, 2, or 3). All participants are required to have been treated with standard-of-care leuprolide acetate or a GnRH receptor antagonist (such as degarelix) in combination with either abiraterone plus prednisone for a minimum of 12 weeks prior to baseline (Day 1) (Part 1), apalutamide for a minimum of 6 weeks prior to baseline (Day1) (Part 2), or docetaxel for a minimum of one treatment cycle (Part 3). Participants will be transitioned from standard-of-care leuprolide acetate or the GnRH receptor antagonist to relugolix; with relugolix treatment initiated the day the next dose of leuprolide acetate or the GnRH antagonist is scheduled for administration with the prior dosing regimen of abiraterone acetate plus a corticosteroid, apalutamide, or docetaxel with or without prednisone being continued.

In addition to evaluating the safety and tolerability of relugolix, the study will also provide safety data as participants transition from injectable leuprolide acetate or degarelix to treatment with relugolix as the androgen-deprivation component of the treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

72 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Three-Part, Open-Label, Parallel-Cohort Safety and Tolerability Study of Relugolix in Combination With Abiraterone Acetate Plus a Corticosteroid, Apalutamide, or Docetaxel With or Without Prednisone in Men With Metastatic Castration-Sensitive Prostate Cancer or Non-Metastatic or Metastatic Castration-Resistant Prostate Cancer

Actual Study Start Date :

Feb 18, 2021

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Relugolix plus Abiraterone plus a Corticosteroid Participants will receive relugolix in combination with abiraterone plus a corticosteroid for 12 weeks during the study treatment period.	Drug: Relugolix (Part 1 and Part 3) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 120-mg dose (1 x 120-mg tablets), taken once daily at approximately the same time each day. (Part 2) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 240-mg dose (2 x 120-mg tablets), taken once daily at approximately the same time each day. Other Names: MVT-601 TAK-385 T-1331285 RVT-601 Orgovyx Drug: Abiraterone Abiraterone acetate (1000 mg [2 x 500-mg tablets]) or fine-particle abiraterone acetate (500 mg [4 x 125-mg tablets]) will be administered orally once daily. Other Names: Zytiga Yonsa Drug: Prednisone (Part 1 only) For participants with mCSPC, a 5-mg dose of prednisone will be administered orally once daily, and for participants with mCRPC, a 5-mg dose of prednisone will be administered orally twice daily. (Part 3 only) Prednisone 5 mg can be administered orally twice daily but is not required. Drug: Methylprednisolone For participants with mCRPC taking fine-particle abiraterone acetate, methylprednisolone 4 mg will be administered orally twice daily. Other Names: Medrol
Experimental: Part 2: Relugolix plus Apalutamide Participants will receive relugolix in combination with apalutamide for 12 weeks during the study treatment period.	Drug: Relugolix (Part 1 and Part 3) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 120-mg dose (1 x 120-mg tablets), taken once daily at approximately the same time each day. (Part 2) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 240-mg dose (2 x 120-mg tablets), taken once daily at approximately the same time each day. Other Names: MVT-601 TAK-385 T-1331285 RVT-601 Orgovyx Drug: Apalutamide Apalutamide 240 mg (4 x 60-mg tablets) will be administered orally once daily. Other Names: Erleada
Experimental: Part 3: Relugolix plus Docetaxel with or without Prednisone Participants will receive relugolix in combination with docetaxel with or without prednisone for 12 weeks during the study treatment period.	Drug: Relugolix (Part 1 and Part 3) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 120-mg dose (1 x 120-mg tablets), taken once daily at approximately the same time each day. (Part 2) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 240-mg dose (2 x 120-mg tablets), taken once daily at approximately the same time each day. Other Names: MVT-601 TAK-385 T-1331285 RVT-601 Orgovyx Drug: Prednisone (Part 1 only) For participants with mCSPC, a 5-mg dose of prednisone will be administered orally once daily, and for participants with mCRPC, a 5-mg dose of prednisone will be administered orally twice daily. (Part 3 only) Prednisone 5 mg can be administered orally twice daily but is not required. Drug: Docetaxel Docetaxel 75 mg/m2 dose will be administered every 3 weeks as a 1-hour intravenous infusion. Other Names: Docefrez Taxotere

Arm

Intervention/Treatment

Experimental: Part 1: Relugolix plus Abiraterone plus a Corticosteroid

Participants will receive relugolix in combination with abiraterone plus a corticosteroid for 12 weeks during the study treatment period.

Drug: Relugolix

(Part 1 and Part 3) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 120-mg dose (1 x 120-mg tablets), taken once daily at approximately the same time each day. (Part 2) Relugolix will be administered orally as a single 360-milligram (mg) loading dose of 3 x 120-mg tablets, followed by a 240-mg dose (2 x 120-mg tablets), taken once daily at approximately the same time each day.

Other Names:

MVT-601

TAK-385

T-1331285

RVT-601

Orgovyx

Drug: Abiraterone

Abiraterone acetate (1000 mg [2 x 500-mg tablets]) or fine-particle abiraterone acetate (500 mg [4 x 125-mg tablets]) will be administered orally once daily.

Other Names:

Zytiga

Yonsa

Drug: Prednisone

(Part 1 only) For participants with mCSPC, a 5-mg dose of prednisone will be administered orally once daily, and for participants with mCRPC, a 5-mg dose of prednisone will be administered orally twice daily. (Part 3 only) Prednisone 5 mg can be administered orally twice daily but is not required.

Drug: Methylprednisolone

For participants with mCRPC taking fine-particle abiraterone acetate, methylprednisolone 4 mg will be administered orally twice daily.

Other Names:

Medrol

Experimental: Part 2: Relugolix plus Apalutamide

Participants will receive relugolix in combination with apalutamide for 12 weeks during the study treatment period.

Drug: Relugolix

Other Names:

MVT-601

TAK-385

T-1331285

RVT-601

Orgovyx

Drug: Apalutamide

Apalutamide 240 mg (4 x 60-mg tablets) will be administered orally once daily.

Other Names:

Erleada

Experimental: Part 3: Relugolix plus Docetaxel with or without Prednisone

Participants will receive relugolix in combination with docetaxel with or without prednisone for 12 weeks during the study treatment period.

Drug: Relugolix

Other Names:

MVT-601

TAK-385

T-1331285

RVT-601

Orgovyx

Drug: Prednisone

Drug: Docetaxel

Docetaxel 75 mg/m2 dose will be administered every 3 weeks as a 1-hour intravenous infusion.

Other Names:

Docefrez

Taxotere

Outcome Measures

Primary Outcome Measures

Incidence of Adverse Events [Baseline through Week 13]
Parts 1, 2, and 3

Secondary Outcome Measures

Mean Testosterone Serum Concentrations at Baseline (Day 1), Week 5, and Week 13 [Baseline (Day 1), Week 5, and Week 13]
Parts 1 and 2
Number and Proportion of Participants with Testosterone Concentrations ≥ 50 ng/dL at Baseline (Day 1), Week 5, and Week 13 [Baseline (Day 1), Week 5, and Week 13]
Parts 1 and 2
Relugolix Trough Concentrations at Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13 [Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13]
Part 2
Apalutamide and N-desmethyl Apalutamide Trough Concentrations at Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13 [Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13]
Part 2
Mean Testosterone Serum Concentrations at Baseline (Day 1), Mid-Treatment, and Week 13 [Baseline (Day 1), Mid-Treatment, and Week 13]
Part 3
Number and Proportion of Participants with Testosterone Concentrations ≥ 50 ng/dL at Baseline (Day 1), Mid-Treatment (Treatment Cycle that Most Closely Corresponds to Week 7 of the Primary Study Treatment Period), and Week 13 [Baseline (Day 1), Mid-Treatment (Treatment Cycle that Most Closely Corresponds to Week 7 of the Primary Study Treatment Period), and Week 13]
Part 3
Relugolix Concentrations at Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel [Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel]
Part 3
Docetaxel Concentrations at Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel [Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel]
Part 3
Incidence of Adverse Events [Up to 52 weeks]
Parts 1, 2, and 3

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Key Inclusion Criteria:

A diagnosis of adenocarcinoma of the prostate confirmed by histologic or cytologic evidence and with a documented medical history of either:

mCSPC (Parts 1, 2, and 3) defined as having at least two of three risk factors at the baseline (Day 1) visit:
Total Gleason score of ≥ 6;
Presence of ≥ 2 metastatic lesions on bone scan;
Evidence of measurable visceral metastases with exception of hepatic metastases.
nmCRPC (Part 2 only) defined as disease progression despite maintaining castration levels of testosterone with androgen deprivation therapy (ADT), as evidenced by an increase in consecutive prostate-specific antigen (PSA) concentrations of ≥ 2 ng/mL (2 measurements, at least one week apart).
mCRPC (Parts 1 and 3) defined as disease progression despite maintaining castration levels of testosterone with ADT:
An increase in PSA ≥ 25% and ≥ 2 ng/mL above the nadir, confirmed by 2 measurements at least 3 weeks apart, and;
The progression of pre-existing disease as evidenced either by worsening symptoms and/or enlarged metastatic lesions; and/or;
The development of new metastases.

Currently receiving standard-of-care treatment of leuprolide acetate (3-, 4-, or 6-month injections [intramuscular Lupron or subcutaneous Eligard]) or a gonadotropin-releasing hormone (GnRH) receptor antagonist (such as degarelix) in combination with:

Part 1: abiraterone acetate 1000 mg or fine-particle abiraterone acetate 500 mg once daily plus prednisone 5 mg once daily for participants with mCSPC or twice daily for participants with mCRPC or methylprednisolone 4 mg once daily and in whom abiraterone has been well tolerated (that is, without evidence of hepatotoxicity requiring dose adjustment for abiraterone) for a minimum of 12 weeks prior to initiation of the study treatment period.
Part 2: apalutamide 240 mg once daily and in whom apalutamide has been well tolerated (that is, without a fracture, fall, or seizure episode or need to dose adjust due to any adverse events) for a minimum of 6 weeks prior to initiation of the study treatment period.
Part 3: docetaxel 75 mg/m2 and in whom docetaxel has been well tolerated (that is, no evidence of hypersensitivity reaction, febrile neutropenia or neutrophils < 500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or moderate neurosensory signs and/or symptoms despite dose reduction) for a minimum of 1 previous treatment cycle.

Key Exclusion Criteria:

Received treatment with a GnRH analog or GnRH receptor antagonist with either abiraterone acetate plus a corticosteroid (Part 1) or apalutamide (Part 2) in mCSPC participants (Parts 1 and 2) or nmCRPC (Part 2) for a total duration > 24 months or in mCRPC participants (Part 1) for a total duration > 6 months.
Abnormal clinical laboratory test value(s) suggestive of clinically unstable underlying disease or a clinical laboratory test value(s) at the screening visit or prior to the baseline (Day 1) visit including:

(Part 1 only) Serum alanine aminotransferase and/or aspartate aminotransferase > upper limit of normal (ULN) (confirmed twice during screening at least 14 days apart);
(Part 3 only) Serum alanine aminotransferase and/or aspartate aminotransferase > 1.5 times ULN concurrently with an alkaline phosphatase > 2.5 times ULN;
(Part 1 only) Total bilirubin > ULN (unless values are consistent with Gilbert's syndrome for which the total bilirubin cannot exceed > 3 times ULN);
(Part 3 only) Total bilirubin > ULN
(Part 1 only) Potassium < 3.5 milliequivalents/liter;
Serum creatinine > 2.0 mg/dL;
Platelets < 100 × 10^3/microliter (μL);
Hemoglobin < 10.0 grams/dL;
Leukocytes < 3 × 10^3/μL;
Absolute neutrophil count < 1.5 × 10^3/μL;
Hemoglobin A1c > 8%.

A medical history within 6 months prior to the screening visit of the following (myocardial infarction; unstable angina; unstable symptomatic ischemic heart disease; New York Heart Association class III or IV heart failure; thromboembolic event[s]), any other significant cardiac conditions, stroke (Part 2 only), transient ischemic attack (Part 2 only), or medical history of seizures (Part 2 only).
An abnormal electrocardiogram finding
Uncontrolled hypertension
Hypotension
Bradycardia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urological Associates of Southern Arizona, P.C.	Tucson	Arizona	United States	85741
2	Arkansas Urology	Little Rock	Arkansas	United States	72211
3	Colorodo Clinical Research	Lakewood	Colorado	United States	80228
4	Chesapeake Urology Research Associates	Baltimore	Maryland	United States	21204
5	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
6	New Jersey Urology	Saddle Brook	New Jersey	United States	07663
7	New Jersey Urology	Voorhees	New Jersey	United States	08043
8	Clinical Research Alliance, Inc.	Westbury	New York	United States	11590
9	Alliance Urology	Greensboro	North Carolina	United States	27403
10	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
11	Clinical Research Solutions	Middleburg Heights	Ohio	United States	44130
12	Center for Advanced Urology, LLP d/b/a: MidLantic Urology	Bala-Cynwyd	Pennsylvania	United States	19004
13	Keystone Urology Specialists	Lancaster	Pennsylvania	United States	17604
14	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
15	Urology Associates, P.C.	Nashville	Tennessee	United States	37209
16	UT Southwestern Medical Center	Dallas	Texas	United States	75390
17	Urology San Antonio	San Antonio	Texas	United States	78229