BMN 673 (Talazoparib), an Oral PARP Inhibitor, in People With Deleterious BRCA1/2 Mutation-Associated Ovarian Cancer Who Have Had Prior PARP Inhibitor Treatment

Recurrent, and/or metastatic germline breast cancer (BRCA) 1/2 mutation-associated ovarian cancer, with progression on a poly (ADP-ribose) polymerase (PARP) inhibitor monotherapy after attaining a response to that PARPi (complete response (CR), partial response (PR), or stable disease (SD) greater than or equal to 4mo)

Progression should have occurred within the immediate prior 2 months of the time of screening visit, with no intervening anti-cancer therapy.

Patients must be at least 4 weeks from the last dose of prior PARP inhibitor.

All patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory baseline biopsy. It is preferred that this lesion be a lesion that progressed or arose while on the prior PARP therapy.

Histopathologic diagnosis of ovarian cancer (including primary peritoneal and fallopian tube cancers) must be confirmed in the Laboratory of Pathology, National Cancer Institute (NCI).

Age greater than or equal to18 years.

Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60%.

Patients must have normal organ and marrow function as defined below:

* absolute neutrophil count greater than or equal to 1,500/mcL

* platelets greater than or equal to100,000/mcL

* total bilirubin less than or equal to 1.5X upper limit of normal, unless known Gilberts syndrome

* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 x institutional upper limit of normal

* creatinine \< 1.5 X upper limit of normal

OR

measured creatinine clearance \>60 mL/min/1.73 m(2) for patients with serum creatinine levels \> 1.5 x upper limit of normal.

hemoglobin greater than or equal to 10 mg/dL (in the absence of transfusion within 24 hours prior to dosing).

* All patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST).

* Use of raloxifene for bone health is allowed.

* Patients must be at least 1 week from the last dose of complementary or alternative medications.

* Patients who have had major surgery must be fully recovered and greater than or equal to 4 weeks postoperative prior to enrolling on study.

* Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study

participation, and for at least three months following the last dose of experimental therapy and must have a negative urine or serum pregnancy test within 7 days prior to the start of the study.

Patient must be able to swallow pills.

Integral biomarkers: all patients who are eligible for the study due to a history of positive BRCA1/2 mutation must provide documented evidence of their deleterious germline mutation status, obtained in a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory, including but not limited to Myriad Genetics prior to study enrollment. Variants of uncertain significance (VUS) of BRCA1/2 and BRCA1/2 somatic mutations are not considered deleterious germline BRCA1/2 mutations. Due to the long acceptance of BRCA 1 and BRCA 2 mutation testing through Myriad, Myriad results will be acceptable. If testing for BRCA 1 and BRCA 2 mutation is done by other organizations, a genetic consultation report from a qualified medical professional confirming that the laboratory results showed a recognized germ line deleterious BRCA 1 or BRCA 2 mutation or deleterious BRCA 1 rearrangement is required.

Ability to understand and the willingness to sign a written informed consent document.

What this study is about