| Eligibility |
Inclusion Criteria:
- Willing and able to provide written informed consent and HIPAA authorization for the
release of personal health information or have their legally authorized representative
provide written informed consent. A signed informed consent must be obtained prior to
performing screening procedures.
NOTE: HIPAA authorization may be either included in the informed consent or obtained
separately
- Males 18 years of age or above
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Bilateral orchiectomy or ongoing androgen deprivation therapy with a GnRH
agonist/antagonist (surgical or medical castration)
- Progression of mCRPC on treatment with at least 1 second generation hormonal agent
(e.g., enzalutamide and/or abirateroneacetate/prednisone)
- Documented progressive mCRPC based on at least one of the following criteria:
- PSA progression defined as at least 2 rises in PSA with a minimum of a 1-week
interval
- 1.0 ng/mL is the minimal starting value if confirmed rise is only indication of
progression
- Soft-tissue progression per RECISTv1.1
- Progression of bone disease (evaluable disease) or tow or more new bone lesions
by bone scan
- Metastatic disease documented by bone lesions on whole-body radionuclide bone scan or
soft tissue disease by computed tomography/magnetic-resonance imaging (CT/MRI).
- Consent to a fresh tumor biopsy during screening or have sufficient archival tumor
tissue available for molecular profile and biomarker analyses
- ECOG status of 0 or 1 (Appendix A: Performance Status Criteria)
- Serum testosterone </= 50mg/dL at screening
- Adequate organ function with acceptable initial laboratory values within 14 days of
treatment start:
Absolute neutrophil count (ANC): >/= 1,500/ul Hemoglobin: >/= 9g/dL Platelet count: >/=
100,00/ul Creatinine: >/= 60 mL/min estimated using the Cockcroft-Gault equation Potassium:
>/= 3.5 mmol/L (within institutional normal range) Bilirubin: </= 1.5 ULN (unless
documented Gilbert's disease) SGOT(AST): </= 2.5 x ULN SGPT (ALT): </= 2.5 x ULN
- Patients must agree to use a highly effective method of contraception (e.g.,
spermicide in conjunction with a barrier such as a condom) or sexual abstinence during
treatment, and for at least 7 months after completing therapy. Furthermore, male
patients with female partners of reproductive potential and pregnant partners must use
a condom (even after vasectomy), during treatment and for at least 4 months after the
final dose. Sperm donation is prohibited during the study and for 30 days after the
last dose of study drug. Female partners must use hormonal or barrio contraception
unless postmenopausal or abstinent.
Exclusion Criteria:
- Prior treatment with a taxane-based chemotherapy for mCRPC (prior treatment with a
taxane-based chemotherapy for metastatic non-castrate prostate cancer is permitted)
- Prior treatment with a PARP inhibitor, platinum, cyclophosphamide, mitozantrone
chemotherapy, ortemozolmide
- Patient has received radiation therapy within 3 weeks (within 2 weeks, if single
fraction of radiotherapy) of treatment start
- Documented carrier of a pathogenic or likely pathogenic germline or somatic mutation
in BRCA 1, BRC 2 or ATM or known carrier (pathogenic or likely pathogenic) or one of
the following DNA Damage Repair genes considered as sensitizing tumors to PARP
inhibitors: FANCA, CHECK2, PALB2, MRE11A, NBN, RAD51C, ATR, MLH1, and CDK12. Testing
is required for BRCA 1, BRCA 1, or ATM. If a patient has had next generation
sequencing that did not include FANCA, CHECK2, PALB2, MRE11A, NBN, RAD51C, ATR, MLH1,
or CDK12 he will not be excluded from the study if status is unknown.
Note, if testing is germline negative, somatic testing is still required. If the patient is
germline positive, the patient is ineligible.
- Use of systemic hormonal (except for GnRH analog), biologic, radium-223, or any
investigational therapy for treatment of metastatic prostate cancer within 4 weeks
prior to treatment start. Exceptions include abiraterone, which may not have been
administered within 2 weeks of treatment start.
- Use of Lutetium (177Lu) vipivotide tetraxetan within 4 weeks prior to treatment start.
- Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus,
or cardiac disease that would, in the opinion of the investigator, make this protocol
unreasonably hazardous to the patient.
- Known or suspected brain metastasis or active leptomeningeal disease.
- Symptomatic or impending spinal cord compression or cauda equine syndrome
- Diagnosis of myelodysplastic syndrome (MDS)
- History of another cancer within 2 years of treatment start 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
- Use of any prohibited concomitant medications (Appendix C: Medications With the
Potential for Drug-Drug Interactions) within 14 days prior to the first dose of
talazoparib
- Grade > 2 treatment-related toxicity unresolved from prior therapy
- Known allergy to any of the compounds under investigation
- Any other condition which, in the opinion of the investigator, would preclude
participation in this trial
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