Study of Talazoparib With Enzalutamide in Men With DDR Gene Mutated mCSPC
Prostate Cancer
Unknown Primary
Summary
The purpose of the study is to evaluate the safety and efficacy of talazoparib in combination
with enzalutamide compared with placebo in combination with enzalutamide in participants with
DDR-deficient mCSPC.
Objectives
The study will have 5 periods: prescreening, screening, double-blind treatment, safety
follow-up, and long-term follow-up.
Approximately 550 men with mCSPC will be randomized. Eligible participants will be randomly
assigned to either of 2 treatment groups as follows:
- Talazoparib in combination with enzalutamide.
- Placebo capsules identical in appearance to talazoparib capsules in combination with
enzalutamide.
Talazoparib or identical placebo treatment will be blinded. Enzalutamide (160 mg/day) will be
open label. The dose of talazoparib/placebo to be given in combination with enzalutamide is
0.5 mg once daily. Participants with moderate renal impairment (eGFR 30-59 mL/min/1.73 m2 by
the MDRD equation) at screening may be enrolled and the talazoparib/placebo dose will be 0.35
mg once daily.
Eligibility
- Male participants at least 18 years of age at screening (20 years for Japan, 19 years for Republic of Korea).
- 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.
- Confirmation of DDR gene mutation status by prospective or historical analysis (with sponsor pre-approval) of blood (liquid biopsy) and/or de novo or archival tumor tissue using FoundationOne Liquid CDx or FoundationOne CDx.
- 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
- 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.
- 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.
- 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.
- Prior treatment of mCSPC with docetaxel is not permitted.
- Treatment with estrogens, cyproterone acetate, or first-generation anti-androgens is allowed until randomization.
- Other prior therapy allowed for mCSPC; =3 months of ADT (chemical or surgical) with or without approved NHT in mCSPC (ie, abiraterone + prednisone, apalutamide, or enzalutamide), if required prior to randomization, with no radiographic evidence of disease progression or rising PSA levels prior to Day 1.
- Participant may have received palliative radiation or surgery for symptomatic control secondary to prostate cancer, which should have been completed at least 2 weeks prior to randomization. NOTE: Radical prostatectomy or definitive radiotherapy to the primary tumor for metastatic castration-sensitive prostate cancer with curative intent is not permitted.
- ECOG performance status 0 or 1.
- Adequate organ function within 28 days before the first study treatment on Day 1, defined by the following:
- ANC =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 <1.5 × ULN (<3 × ULN for participants with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).
- AST or ALT <2.5 × ULN (<5 × ULN if liver function abnormalities are due to hepatic metastasis).
- Albumin >2.8 g/dL.
- eGFR =30 mL/min/1.73 m2 by the MDRD equation.
- Sexually active participants that in the opinion of the investigator are capable of ejaculating, must agree to use a condom when having sex with a partner (female or male) from the time of the first dose of study treatment through 4 months after last dose of study treatment (or, if talazoparib/placebo has been stopped more than a month earlier than enzalutamide, through 3 months after last dose of enzalutamide). 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 (or, if talazoparib / placebo has been stopped more than a month earlier than enzalutamide, through 3 months after last dose of enzalutamide) when having sex.
- Must agree not to donate sperm from the first dose of study treatment to 4 months after the last dose of study treatment (or, if talazoparib/placebo has been stopped more than a month earlier than enzalutamide, through 3 months after last dose of enzalutamide).
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including being able to manage electronic diaries. The PRO assessments are not required to be completed if a patient does not understand the language(s) available for a specific questionnaire and/or cannot complete the specific questionnaire independently.
- Capable of giving signed informed consent.
- For France only: Participants affiliated with the social security system or beneficiaries of an equivalent system.
Treatment Sites in Georgia
340 Kennestone Hospital Boulevard
Suite 200
Marietta, GA 30060
770-281-5131
www.ngoc.com
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