Metastatic Castration-resistant Prostate Cancer MedDRA version: 27.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. At least 18 years of age. For Japan, at least 20 years of age. 2. Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell or signet cell features. If the patient does not have a prior histological diagnosis, a baseline de novo biopsy must be used to confirm the diagnosis and to support biomarker analysis. 3. Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) (score on BPI-SF Question #3 must be <4). 4. For enrollment into Part 2 only (optional in Part 1): assessment of DDR mutation status by prospective analysis of blood (liquid biopsy), or tissue (de novo or archival tissue), or historical analysis (with Sponsor pre-approval), of most recent tumor tissue per FoundationOne testing. (Note: for patients enrolling in Part 1, DDR deficiency testing is optional). 5. For enrollment into Part 2 only (optional for Part 1): 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. Surgically or medically castrated, with serum testosterone =50 ng/dL (=1.73 nmol/L) at screening. Ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist for patients who have not undergone bilateral orchiectomy must be initiated at least 4 weeks before Day 1 (Part 1) or randomization (Part 2) and must continue throughout the study. 7. Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI scan. Scans obtained as part of standard of care in the 6 weeks (42 days) prior to Day 1 (Part 1) or randomization (Part 2) can be used if they meet study requirements (Table 2). Measurable soft tissue disease is not required. (Adenopathy below the aortic bifurcation alone does not qualify). 8. Progressive disease at study entry in the setting of medical or surgical castration as defined by 1 or more of the following 3 criteria: - Prostate specific antigen (PSA) progression defined by rising PSA of at least 2 consecutive rises in most recent PSA to be documented over a reference value (measure 1) taken at least 7 days apart within the last 12 months. If the third PSA measure is not greater than the second measure, a fourth PSA measure is required to be taken and be greater than the second measure. The third (or the fourth) confirmatory PSA should be taken within 4 weeks prior to randomization. The third (or the fourth) PSA value, obtained before randomization must be = 1 µg/L if qualifying only by PSA progression. - Soft tissue disease progression as defined by RECIST 1.1. - Bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or more new metastatic bone lesions on a whole body radionuclide bone scan. 9. Ongoing bisphosphonate or denosumab use prior to Day 1 (Part 1) or randomization (Part 2) is allowed but not mandatory. 10. Eastern Cooperative Oncology Group (ECOG) performance status =1. 11. Life expectancy ?12 months as assessed by the investigator. 12. Able to swallow the study treatment and have no known intolerance to study treatments or excipients. 13. Sexually active participants that in the opinion of the investigator are capable of ejacu
Exclusion criteria
Exclusion criteria: Patients with any of the following characteristics/conditions will be excluded: 1. Any prior systemic cancer treatment initiated in the non-metastatic CRPC and mCRPC disease state. (ADT and first generation antiandrogens received in the CRPC disease state are NOT exclusionary.) 2. Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation. 3. Prior treatment with second-generation androgen receptor inhibitors (enzalutamide, apalutamide, and darolutamide), a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer. 4. 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). •Prior docetaxel for mCSPC is allowed if more than 4 weeks have elapsed from the last dose of docetaxel. 5. Treatment with cytotoxic chemotherapy which includes but is not limited to docetaxel, 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). Prior treatment with abiraterone in the castration-sensitive settings is not exclusionary if discontinued prior to randomization. Hormonal therapy (eg, bicalutamide, nilutamide, flutamide, estrogens) are not exclusionary if discontinued prior to randomization. *Prednisone >10 mg/day (or equivalents) is exclusionary. 6. Treatment with any investigational agent within before Day 1 (Part 1) or randomization (Part 2). 7. 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). 8. Current use of potent P-gp inhibitors within 7 days prior to Day 1 (Part 1) or randomization (Part 2.) For a list of potent P-gp inhibitors, and other medications which are exclusionary because of interaction with either talazoparib or enzalutamide, refer to Section 5.9. 9. 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). 10. Clinically significant cardiovascular disease, including any of the following: - Myocardial infarction or symptomatic cardiac ischemia within 6 months before Day 1 (Part 1) or randomization (Part 2). - Congestive heart failure New York Heart Association class III or IV. - History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes) within 1 year before screening. - History of Mobitz II second degree or third degree heart block unless a permanent pacemaker is in place. - Hypotension as indicated by systolic blood pressure 170 mm Hg or diastolic blood pressure >105 mm Hg at screening. However, patients can be rescreened after adequate control of blood pressure is achieved. Please refer to protocol for the full list of exclusion criteria.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To demonstrate that talazoparib in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging blinded independent central review (BICR) assessed rPFS, in patients with mCRPC unselected for DDR status. - To demonstrate that talazoparib in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging BICR assessed rPFS, in patients with mCRPC harboring DDR deficiencies.;Secondary Objective: Key Secondary Objectives: - To demonstrate that talazoparib in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging OS in patients with mCRPC unselected for DDR status. - To demonstrate that talazoparib in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging OS in patients with mCRPC harboring DDR deficiencies. Other Secondary Objectives: - To evaluate anti-tumor activity in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies with respect to the following: - BICR assessed objective response in measurable soft tissue disease; - BICR assessed duration of response in measurable soft tissue disease; - PSA response; - Time to PSA progression; - Time to initiation of cytotoxic chemotherapy; - Time to initiation of antineoplastic therapy; See the protocol for additional objectives. ;Primary end point(s): - BICR assessed rPFS per RECIST 1.1 (soft tissue disease) and PCWG3 (bone disease) in patients with mCRPC unselected for DDR status. - BICR assessed rPFS per RECIST 1.1 (soft tissue disease) and PCWG3 (bone disease) in patients with mCRPC harboring DDR deficiencies. ;Timepoint(s) of evaluation of this end point: As per protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoints: - OS in patients with mCRPC unselected for DDR status (alpha-protected). - OS patients with mCRPC harboring DDR deficiencies (alpha-protected). Other Secondary Endpoints: - Proportion of patients with measurable soft tissue disease at baseline with an objective response per RECIST 1.1 (assessed by the BICR) in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Duration of soft tissue response per RECIST 1.1 (assessed by the BICR) in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Proportion of patients with PSA response =50% in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Time to PSA progression in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Time to initiation of cytotoxic chemotherapy in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Time to initiation of antineoplastic therapy in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Time to first symptomatic skeletal event in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - PFS2 based on investigator assessment separately in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Time to opiate use for prostate cancer pain in patients with mCRPC unselected for DDR status and in patients with mCRPC harboring DDR deficiencies. - Incidence of adverse events characterized by type, severity (graded by NCI CTCAE version 4.03), timing, seriousness and relationship to study treatment. - PK characterized by pre-dose trough and post-dose plasma concentrations of talazoparib, enzalutamide and its N-desmethyl metabolite. - PROs in patients w | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Korea, Republic of, New Zealand, Norway, Peru, Poland, Portugal, South Africa, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed