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


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; and
  • Presence of ≥ 2 metastatic lesions on bone scan; OR
  • Radiologic 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 (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 consecutive PSA (2 measurements at least 1 weeks apart);
  • Worsening clinical symptoms;
  • Radiologic evidence demonstrating enlarged metastatic lesions 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).
  • 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).
  • 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).

Key Exclusion Criteria:

  • A patient will not be eligible for inclusion in the study if any of the following criteria apply: 1. A medical history of brain or hepatic metastases based on radiologic evidence or a medical history of surgical castration; 2. Received combination treatment with a GnRH analog or GnRH receptor antagonist with either abiraterone acetate plus a corticosteroid (Part 1) or apalutamide (Part 2) in patients with mCSPC (Part 1 and Part 2) or nmCRPC (Part 2) for a total duration > 24 months or in patients with mCRPC (Part 1) for a total duration > 6 months; 3. Is scheduled or anticipates being scheduled for major surgery during the study treatment period; 4. A current diagnosis of a malignancy other than prostate cancer, with the exception of any of the following:
  • Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of any type;
  • Adequately treated Stage I cancer that is currently in remission and has been in remission for ≥ 2 years;
  • Any other cancer from which the patient has been disease-free for ≥ 3 years; 5. Abnormal clinical laboratory test value(s) at the screening visit or prior to the baseline (Day 1) visit including:
  • Serum creatinine > 2.0 mg/dL;
  • Platelets < 100 × 103/μL;
  • Hemoglobin < 10.0 g/dL;
  • Leukocytes (WBC) < 3 × 103/μL;
  • Absolute neutrophil count < 1.5 × 103/μL;
  • Hemoglobin A1c (HbA1c) > 8%; Note (Part 3 only): Transfusions and/or administration of growth factors are permitted as indicated for the clinical management of docetaxel-related hematologic effects and in accordance with the investigator's judgement. 6. Known hepatic disease, including alcoholic liver disease or viral hepatitis such as hepatitis A (hepatitis A virus IgM positive), chronic hepatitis B (HbsAg positive), or chronic hepatitis C (HCV antibody positive, confirmed by HCV RNA) or clinical signs of hepatic disease such as jaundice; 7. A medical history within 6 months prior to the screening visit or a current diagnosis of any of the following:
  • Myocardial infarction;
  • Unstable angina;
  • Unstable symptomatic ischemic heart disease;
  • Congestive heart failure classified as NYHA class III or IV heart failure;
  • Thromboembolic event(s) (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular event[s]);
  • Any other significant cardiac condition (eg, pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease); 8. An abnormal ECG 9. Uncontrolled hypertension 10. Hypotension 11. Bradycardia 12. Positive HIV 13. Medical history of a bleeding disorder or current clinical evidence of gastrointestinal bleeding or active bleeding from another anatomical location. 14. A medical history within 1 year of the screening visit of drug or alcohol abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders V 15. Received an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to the baseline (Day 1) visit; 16. Prior use of any prohibited medication(s) and restrictive medication(s) without the appropriate washout period or use of a prohibited medication during the study treatment period is planned; 17. A contraindication or known history of hypersensitivity to any of the study treatments or components thereof, or has a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates study participation; 18. Any other medical or psychiatric condition that, in the opinion of the investigator, would interfere with accomplishing the study objectives or the patient completing the study; 19. Is a study site employee or is a primary family member (spouse, parent, child, or sibling) of a site employee involved in the conduct of the study.

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