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

• ClinicalTrials.gov Identifier: NCT04666129
• Recruitment Status: Recruiting
• First Posted: December 14, 2020
• Last Update Posted: June 2, 2022
• Sponsor: Myovant Sciences GmbH
• Information provided by (Responsible Party): Myovant Sciences GmbH

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 (Clinical Trial)
• Estimated 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: February 18, 2021
• Estimated Primary Completion Date: January 2023
• Estimated Study Completion Date: November 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 Name: 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 Name: 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Mean Testosterone Serum Concentrations at Baseline (Day 1), Week 5, and Week 13 [ Time Frame: Baseline (Day 1), Week 5, and Week 13 ]
   Parts 1 and 2
2. Number and Proportion of Participants with Testosterone Concentrations ≥ 50 ng/dL at Baseline (Day 1), Week 5, and Week 13 [ Time Frame: Baseline (Day 1), Week 5, and Week 13 ]
   Parts 1 and 2
3. Relugolix Trough Concentrations at Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13 [ Time Frame: Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13 ]
   Part 2
4. Apalutamide and N-desmethyl Apalutamide Trough Concentrations at Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13 [ Time Frame: Baseline (Day 1), Week 3, Week 5, Week 9, and Week 13 ]
   Part 2
5. Mean Testosterone Serum Concentrations at Baseline (Day 1), Mid-Treatment, and Week 13 [ Time Frame: Baseline (Day 1), Mid-Treatment, and Week 13 ]
   Part 3
6. 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 [ Time Frame: 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
7. Relugolix Concentrations at Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel [ Time Frame: Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel ]
   Part 3
8. Docetaxel Concentrations at Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel [ Time Frame: Baseline (Day 1), In-Cycle, Mid-Treatment, and Week 13 in Each Infusion Cycle for Docetaxel ]
   Part 3
9. Incidence of Adverse Events [ Time Frame: Up to 52 weeks ]
   Parts 1, 2, and 3

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. 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.

2. 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:

1. 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.

2. 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%.
3. 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).
4. An abnormal electrocardiogram finding
5. Uncontrolled hypertension
6. Hypotension
7. Bradycardia

Contacts and Locations

Contacts

Contact: Clinical Trials at Myovant; 650-278-8743; ClinicalTrials@Myovant.com

Locations

United States, Arizona

Urological Associates of Southern Arizona, P.C.; Recruiting

Tucson, Arizona, United States, 85741

United States, Colorado

Colorodo Clinical Research; Recruiting

Lakewood, Colorado, United States, 80228

United States, Maryland

Chesapeake Urology Research Associates; Recruiting

Baltimore, Maryland, United States, 21204

United States, North Carolina

Alliance Urology; Recruiting

Greensboro, North Carolina, United States, 27403

Wake Forest Baptist Health; Recruiting

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Clinical Research Solutions; Recruiting

Middleburg Heights, Ohio, United States, 44130

United States, Pennsylvania

Center for Advanced Urology, LLP d/b/a: MidLantic Urology; Recruiting

Bala-Cynwyd, Pennsylvania, United States, 19004

Keystone Urology Specialists; Recruiting

Lancaster, Pennsylvania, United States, 17604

United States, South Carolina

Carolina Urologic Research Center; Recruiting

Myrtle Beach, South Carolina, United States, 29572

United States, Tennessee

Urology Associates, P.C.; Recruiting

Nashville, Tennessee, United States, 37209

United States, Texas

Urology San Antonio; Recruiting

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Myovant Sciences GmbH

Investigators

• Study Director: Myovant Medical Monitor; Myovant Sciences

More Information

• Responsible Party: Myovant Sciences GmbH
• ClinicalTrials.gov Identifier: NCT04666129
• Other Study ID Numbers: MVT-601-049
• First Posted: December 14, 2020
• Last Update Posted: June 2, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Myovant Sciences GmbH:

mCRPC; mCSPC; Relugolix; Abiraterone; Prednisone; Leuprolide acetate; nmCRPC; Apalutamide; Docetaxel; Degarelix; Methylprednisolone

Additional relevant MeSH terms:

Prostatic Neoplasms; Hypersensitivity; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Immune System Diseases; Prednisone; Methylprednisolone; Docetaxel; Relugolix; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Neuroprotective Agents; Protective Agents; Androgen Antagonists