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

• Status: Recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: Male

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Myovant Sciences GmbH
• Treatments: Docetaxel; Methylprednisolone; Prednisone; Relugolix

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