Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer Who Previously Received Taxane-Based Chemotherapy and Progressed on at Least 1 Novel Hormonal Agent (Enzalutamide and/or Abiraterone Acetate/Prednisone) MedDRA version: 21.1 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: Castra
Conditions
Interventions
Product Name: Talazoparib
Product Code: PF-06944076
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Talazoparib
CAS Number: 1373431-65-2
Current Sponsor code: PF-06944076
Other descriptive na
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1.For patients who are at least 18 years of age, there must be evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. 2.Histologically or cytologically confirmed adenocarcinoma of the prostate without signet cell, or small cell features. Histologic confirmation may be based on a de novo tumor biopsy obtained for purposes of screening. Biopsies of the brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel may not be performed for the sole purpose of determining study eligibility. 3.Patients must have measurable soft tissue disease per RECIST1.1. 4.DNA damage repair gene alterations likely to sensitize to PARP inhibition (DDR positive) as determined by: •Prospective testing of de novo or archival tumor tissue (via central laboratory) or prior historical (with Sponsor preapproval) testing of tumor tissue using the Foundation Medicine, FoundationOne® NGS gene panel test; Archival or de novo tumor tissue also should be submitted prior to Day 1 if possible to support concordance analyses and additional molecular profiling. 5.Unless prohibited by local regulations or ethics committee (EC) decision, consent to a saliva sample collection for retrospective sequencing of DDR genes used to assess patient eligibility based on tumor tissue, and to serve as a germline control in identifying tumor mutations. 6.Serum testosterone = 1.73 nmol/L (50 ng/dL) at screening. 7.Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist (surgical or medical castration). 8.Progressive disease at study entry defined as 1 or more of the following 3 criteria: •A minimum of 3 rising PSA values with an interval of at least 1 week between determinations. The screening central laboratory PSA value must be = 2 µg/L (2 ng/mL) if qualifying solely by PSA progression. •Soft tissue disease progression as defined by RECIST 1.1. •Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions on bone scan. 9.Metastatic disease. Patients whose only evidence of metastasis is measurable soft tissue disease below the aortic bifurcation will be acceptable. Neither bone metastases on bone scan nor non- measurable soft tissue disease alone will qualify a patient. 10.Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane based regimen for metastatic (non castrate or castrate) prostate cancer. Patients may have received radium 223 and/or cabazitaxel, or were deemed unsuitable, declined, or did not have access to these therapies. 11.Documented disease progression (either radiographic or biochemical) on at least 1 novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate prostate cancer or nonmetastatic (M0) CRPC. 12.Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before day 1 for patients receiving these therapies. 13.ECOG performance status of 0 to 2. 14.Estimated life expectancy of = 6 months as assessed by the investigator. 15.Able to swallow the study drug, have no known intolerance to study drugs or excipients, and comply with study requirements. 16.Must use a condom when having sex with a pregnant woman from the time of the first dose of study drug through 105
Exclusion criteria
Exclusion criteria: 1.Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist) or any other investigational agent within 4 weeks before day 1. 2.Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy. Patients who discontinued prior platinum based chemotherapy ? 6 months prior to screening or whose disease previously progressed on platinum based therapy at any time in the past are also excluded. 3.Treatment with any concurrent cytotoxic chemotherapy or investigational drug(s) within 4 weeks or 5 half lives of the drug (whichever is longer) before Day 1 and/or during study participation. 4.Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy) before day 1. 5.Major surgery within 2 weeks before day 1. 6.Clinically significant cardiovascular disease, including any of the following: •Myocardial infarction or symptomatic cardiac ischemia within 6 months before screening. •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. 7.Significant organ dysfunction as defined by any one of the following laboratory abnormalities: •Renal: eGFR 1.5 times the upper limit of normal (ULN) (> 3 × ULN for patients with 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 (if liver test abnormalities are due to hepatic metastasis, then AST or ALT = 5 × ULN); •Albumin < 2.8 g/dL. •Bone marrow reserve: absolute neutrophil count < 1500/µL, platelets < 100,000/µL, or hemoglobin < 9 g/dL (NOTE: may not have received growth factors or blood transfusions within 14 days before obtaining the hematology values at screening). 8.Known or suspected brain metastasis or active leptomeningeal disease. 9.Symptomatic or impending spinal cord compression or cauda equina syndrome. 10.Diagnosis of myelodysplastic syndrome. 11.History of another cancer within 3 years before enrollment with the exception of nonmelanoma skin cancers, or 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. 12.Gastrointestinal disorder affecting absorption. 13.Current or anticipated use of the following P gp inhibitors (amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, verapamil, and val
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of single agent talazoparib in DNA damage repair (DDR) + metastatic CRPC, as measured by best objective response rate (ORR).;Secondary Objective: To evaluate efficacy with respect to the following parameters: -Time to objective response; -Duration of response; -Proportion of patients with prostate-specific antigen (PSA) decrease = 50%; -Proportion of patients with conversion of circulating tumor cell (CTC) count; -Time to PSA progression; -Radiographic progression-free survival (PFS); -Overall survival. To evaluate the safety of talazoparib in this patient population. To evaluate the following patient-reported outcomes: -Time to deterioration in pain as assessed by the Brief Pain Inventory Short Form (BPI-SF); -Change from baseline in pain per BPI-SF; -Change from baseline in general health status as assessed by the European Quality of Life 5-Domain 5-Level Scale (EQ-5D-5L). To evaluate the pharmacokinetics (PK) of talazoparib;Primary end point(s): Best objective response rate (ORR).The proportion of patients with a best overall soft tissue response of CR or PR per RECIST 1.1 ;Timepoint(s) of evaluation of this end point: The primary endpoint analysis will be performed when the last enrolled patient completes at least 6 months of study drug treatment, withdraws consent, discontinues from the study, or dies, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: - Time to objective response: time from first dose of talazoparib to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. - Duration of response: time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST 1.1 by independent central review and no evidence of confirmed bone disease progression per PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occurs first. -CTC assessment at weeks 1,9,17,25, safety follow up -PSA assessment at weeks 1,9,13,17,21,25, safety follow up;Secondary end point(s): - Time to objective response - Duration of response - Proportion of patients with conversion of CTC count - Time to PSA progression | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Denmark, France, Germany, Hungary, Italy, Korea, Republic of, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial.gov Call Centre
Pfizer Inc.
Outcome results
None listed