A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF TALAZOPARIB WITH ENZALUTAMIDE IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF TALAZOPARIB WITH ENZALUTAMIDE IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
This study compares rPFS in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.
Part 1 is an open-label, non-randomized, safety and PK run-in study designed to confirm the starting dose of talazoparib in combination with enzalutamide through assessment of target safety events and PK at select sites. Part 2 is a randomized, double-blind, placebo-controlled, multinational study comparing talazoparib plus enzalutamide vs. placebo plus enzalutamide in patients with mCRPC.
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell or signet cell features
Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) (score on BPI-SF Question #3 must be < 4).
For enrollment into Part 2 only (optional in Part 1): assessment of DDR mutation status
Consent to a saliva sample collection for a germline comparator unless prohibited by local regulations or ethics committee decision (optional for patients in Part 1).
Surgically or medically castrated, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI scan.
Progressive disease at study entry in the setting of medical or surgical castration as defined by 1 or more of the following 3 criteria:
Ongoing bisphosphonate or denosumab use prior to Day 1 (Part 1) or randomization (Part 2) is allowed but not mandatory.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Life expectancy ≥ 12 months as assessed by the investigator.
Able to swallow the study drug and have no known intolerance to study drugs or excipients.
Must agree to use a condom when having sex with a partner from the time of the first dose of study drug through 4 months after last dose of study treatment. Must also agree for female partner of childbearing potential to use an additional highly effective form of contraception from the time of the first dose of study treatment through 4 months after last dose of study treatment when having sex with a non pregnant female partner of childbearing potential.
Must agree not to donate sperm from the first dose of study drug to 4 months after the last dose of study drug.
Evidence of a personally signed and dated informed consent document (and molecular prescreening consent if appropriate) indicating that the patient [or a legally acceptable representative/legal guardian] has been informed of all pertinent aspects of the study.
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion Criteria:
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:
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 any of the following:
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).
Anchorage, Alaska 99503, United States
Chandler, Arizona 85224, United States
Gilbert, Arizona 85297, United States
Scottsdale, Arizona 85260, United States
Loma Linda, California 92350, United States
Loma Linda, California 92354, United States
Rancho Mirage, California 92270, United States
Portland, Oregon 97225, United States
Nashville, Tennessee 37232, United States
Pergamino, Buenos Aires B2700CPM, Argentina
Caba, C1280AEB, Argentina
Caba, C1431FWO, Argentina
Rio de Janeiro, Rio de Janeiro 20230-130, Brazil
Rio de Janeiro, Rio de Janeiro 20231-050, Brazil
Rio de Janeiro, Rio de Janeiro 20551-030, Brazil
Lajeado, Rio Grande do Sul 95900-022, Brazil
Porto Alegre, Rio Grande do Sul 90610-000, Brazil
Porto Alegre, Rio Grande do Sul 91350-200, Brazil
Santo André, São Paulo 09060-650, Brazil
Santo André, São Paulo 09060-870, Brazil
São Paulo, SÃO Paulo (SP) 01246-000, Brazil
Chicoutimi, Quebec G7H 5H6, Canada
Chicoutimi, Quebec G7H 7K9, Canada
Sherbrooke, Quebec J1H 5N4, Canada
Santiago, Santiago Metropolitan 7500713, Chile
Araucania, 4800827, Chile
Wuhan, Hubei 430022, China
Wuhan, Hubei 430030, China
Nanjing, Jiangsu 210008, China
Shanghai, 200025, China
Ostrava-Poruba, 708 52, Czechia
Meldola, FC 47014, Italy
Trento, Trentino-Alto Adige 38122, Italy
Kure, Hiroshima 737-0023, Japan
Meguro-ku, Tokyo 152-8902, Japan
Shinjuku-ku, Tokyo 160-8582, Japan
Lorenskog, 1478, Norway
Brzozów, 36-200, Poland
Seoul, 03722, South Korea
Santiago de Compostela, A Coruna 15706, Spain
Glasgow, Scotland G12 0XH, United Kingdom
Cornwall, TR1 3LJ, United Kingdom
Glasgow, G12 0YN, United Kingdom