| CRITÈRES D'EXCLUSION |
(EN)
- Any prior systemic cancer treatment initiated in in the non metastatic CRPC and mCRPC disease state.
- Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.
- Prior treatment with second-generation androgen receptor inhibitors (enzalutamide, apalutamide, and darolutamide), a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer.
- Prior treatment with platinum-based chemotherapy within 6 months (from the last dose) prior to Day 1 (Part 1) or randomization (Part 2), or any history of disease progression on platinum-based therapy within 6 months (from the last dose).
- Treatment with cytotoxic chemotherapy, biologic therapy including sipuleucel T, or radionuclide therapy received in the castration-sensitive prostate cancer is NOT exclusionary if discontinued in the 28 days prior to Day 1 (Part 1) or randomization (Part 2).
- Treatment with any investigational agent within 4 weeks before Day 1 (Part 1) or randomization (Part 2).
- Prior treatment with opioids for pain related to either primary prostate cancer or metastasis within 28 days prior to Day 1 (Part 1) or randomization (Part 2).
- Current use of potent P-gp inhibitors within 7 days prior to Day 1 (Part 1) or randomization (Part 2).
- Major surgery (as defined by the investigator) within 2 weeks before Day 1 (Part 1) or randomization (Part 2), or palliative localized radiation therapy within 3 weeks before randomization (Part 2).
- Clinically significant cardiovascular disease
- Significant renal dysfunction as defined by any of the following laboratory abnormalities:
- • Renal: eGFR < 30 mL/min/1.73 m2 by the MDRD equation (available via www.mdrd.com).
- Patients enrolled in Part 1 only: Moderate renal impairment (eGFR 30-59 mL/min/1.73 m2) at screening.
- Significant hepatic dysfunction as defined by any of the following laboratory abnormalities on screening labs:
- Total serum bilirubin >1.5 times the upper limit of normal (ULN) (>3 × ULN for patients with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times ULN (>5 × ULN if liver function abnormalities are due to hepatic metastasis).
- Albumin <2.8 g/dL
- Absolute neutrophil count < 1500/µL, platelets < 100,000/µL, or hemoglobin < 9 g/dL (may not have received growth factors or blood transfusions within 14 days before obtaining the hematology values at screening).
- Known or suspected brain metastasis or active leptomeningeal disease.
- Symptomatic or impending spinal cord compression or cauda equina syndrome.
- Any history of myelodysplastic syndrome, acute myeloid leukemia, or prior malignancy except for the following:
- Carcinoma in situ or non melanoma skin cancer
- A cancer diagnosed and treated ≥ 5 years before randomization with no subsequent evidence of recurrence
- American Joint Committee on Cancer Stage 0 or Stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the sponsor
- Gastrointestinal disorder affecting absorption.
- Fertile male subjects who are unwilling or unable to use highly effective methods of contraception for the duration of the study and for 4 months after the last dose of investigational product.
- Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
- Other acute or chronic medical (concurrent disease, infection, or comorbidity) or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that interferes with ability to participate in the study, may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma). Also, history of loss of consciousness or transient ischemic attack within 12 months of randomization (Part 2).
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