A Phase 1, Open-Label, Single-Cohort Safety and Tolerability Study of Relugolix in Combination With Abiraterone Plus Prednisone in Men With High-Risk Metastatic Castration-Sensitive Prostate Cancer or Metastatic Castration-Resistant Prostate Cancer Being

Condition: Metastatic Castration-Resistant Prostate Cancer, Metastatic Castration-Sensitive Prostate Cancer, Non-Metastatic Castration-Resistant Prostate Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04666129

Sponsor: Myovant Sciences GmbH

Phase: Phase 1

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: Male

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

View trial on ClinicalTrials.gov