castration sensitive Prostate cancer
Conditions
Interventions
Eligible participants will be randomly assigned to either of 2 treatment groups
as follows:
* 0.5 gr once daily Talazoparib in combination with enzalutamide.
* Placebo capsules identical in appearanc
Sponsors
Pfizer
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age and Sex: 1.Male participants at least 18 years of age at screening (Refer to Appendix 9 of the protocol for Japan and Republic of Korea) . Type of Participant and Disease Characteristics: 2.Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, small cell or signet cell features. If the participant does not have a prior histological diagnosis, a baseline de novo biopsy must be used to confirm the diagnosis and may also be used to support biomarker analysis. 3.Confirmation of DDR gene mutation status (as per the genes included in DDR12 panel described in Table 6) by prospective or historical analysis (with sponsor pre-approval) of blood (liquid biopsy) and/or de novo or archival tumor tissue using FoundationOne® CDx or FoundationOne CDx®. 4.Willing to provide tumor tissue when available (de novo or archived) for retrospective molecular profiling analysis, if not already provided as part of inclusion criterion 3. 5.Unless prohibited by local regulations or ethics committee decision, consent to a saliva sample collection for retrospective sequencing of the same DDR genes tested on tumor tissue and blood (liquid biopsy), or a subset thereof, and to serve as a germline control in identifying tumor mutations. 6. Ongoing ADT with a GnRH agonist or antagonist for participants who have not undergone bilateral orchiectomy must be initiated before randomization and must continue throughout the study. 7.Metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on CT or MRI scan (for soft tissue). Participants whose disease spread is limited to regional pelvic lymph nodes are not eligible. Note: a finding of superscan at baseline is exclusionary. Allowed Prior Treatments: 8.Note: prior treatment of mCSPC with docetaxel is no longer permitted. 9.Treatment with estrogens, cyproterone acetate, or first-generation anti-androgens is allowed until randomization. 10.Other prior therapy allowed for mCSPC; =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 laboratory tests at screening). •Total serum bilirubin 2.8 g/dL. •eGFR >=30 mL/min/1.73 m2 by the MDRD equation, see Appendi
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions: 1.Other acute or chronic medical [concurrent disease, infection, including chronic stable HIV, HBV, or HCV infection (refer to Appendix 13 of the protocol), or co-morbidity] or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that interferes with a participant's ability to participate in the study, may increase the risk of associated with study participation or study treatment administration, or may interfere with the interpretation of study results, and, in the investigator's judgment, make the participant inappropriate for entry into the study. HIV/HBV/HCV testing is not required unless mandated by local health authority. 2.History of seizure or any condition (as assessed by investigator) that may predispose to seizure (eg, prior cortical stroke, significant brain trauma), including any history of loss of consciousness or transient ischemic attack within 12 months of randomization. 3.Major surgery (as defined by the investigator) within 2 weeks before randomization. 4.Known or suspected brain metastasis or active leptomeningeal disease. 5.Symptomatic or impending spinal cord compression or cauda equina syndrome. 6.Any history of MDS, AML, or prior malignancy except for the following: •Carcinoma in situ or non-melanoma skin cancer. •A cancer diagnosed and treated >=3 years before randomization with no subsequent evidence of recurrence. •American Joint Committee on Cancer Stage 0 or Stage 1 cancer 170 mm Hg or diastolic blood pressure >105 mm Hg at screening. However, participants can be rescreened after adequate control of blood pressure is achieved. 9.Active COVID-19 infection detected by viral test or based on clinical diagnosis (as assessed by investigator). Asymptomatic participants with no active COVID-19 infection detected but positive antibody tests, indicating past infection are allowed. Prior/Concomitant Therapy: 10.Prior ADT in the adjuvant/neoadjuvant setting, where the completion of ADT was less than 12 months prior to randomization and the total duration of ADT exceeded 36 months. 11.Participant received treatment with systemic glucocorticoids greater than the equivalent of 10 mg per
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Investigator-assessed rPFS per Response Evaluation Criteria in Solid Tumors (RECIST 1.1 [soft tissue disease]) and Prostate Cancer Working Group (PCWG3 [bone disease]) in participants with mCSPC harboring DDR deficiencies. | — |
Secondary
| Measure | Time frame |
|---|---|
| - OS in participants with mCSPC harboring DDR deficiencies (alpha-protected). - Proportion of participants with measurable soft tissue disease at baseline with an objective response per RECIST 1.1. - Duration of soft tissue response per RECIST 1.1. - Proportion of participants with PSA response 50% in participants with detectable PSA values at baseline. - Time to PSA progression. - Time to initiation of antineoplastic therapy. - Time to first symptomatic skeletal event. - Time to opioid use for prostate cancer pain. - Incidence of adverse event (AEs) characterized by type, severity (graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.03), timing, seriousness and relationship to study intervention. - Predose trough plasma concentrations of talazoparib, enzalutamide and its N-desmethyl metabolite - Change from baseline in participant-reported pain symptoms per Brief Pain Inventory Short Form (BPI-SF); - Change from baseline in participant-reported general health status per European Quality of Life 5 Dimension, 5 Level Scale EQ-5D-5L; - Change from baseline in participant-reported cancer - specific global health status/ quality of life (QoL), functioning, and symptoms per European Organisation for Research and Treatment of Cancer cancerspecific global health questionnaire (EORTC QLQ-C30); - Time to deterioration in participant-reported pain symptoms per BPI-SF; - Time to definitive deterioration in participant-reported global health status/QoL per EORTC QLQ-C30; - Time to definitive deterioration in participant-reported disease specific urinary symptoms per European Organisation for Research and Treatment of Cancer disease-specific urinary symptoms questionnaire (EORTC QLQPR25). - Change from baseline in patient global impression of severity (PGI-S). - ctDNA burden at baseline and on study, as assessed using FoundationOne® liquid or another suitable validated assay. | — |
Countries
Netherlands
Outcome results
None listed