Talazoparib in Determining Genetic Effects on Disease Response in Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

PRIMARY OBJECTIVES:

I. To explore basal levels and effects of talazoparib (BMN 673) on DNA copy number, loss of
heterozygosity and mutation, and level of ribonucleic acid (RNA) and protein expression
(together described as "molecular results") in homologous recombination-related pathways
before and after treatment in women with primary advanced high grade serous ovarian,
fallopian tube, or primary peritoneal cancer.

SECONDARY OBJECTIVES:

I. To correlate molecular results to clinical endpoints including response and survival.

II. To correlate molecular results to pathologic endpoints including tumor volume and
apoptosis.

III. To compare DNA copy number and level of RNA and protein expression in homologous
recombination-related pathways in tissue from patients treated with BMN 673 to those
untreated with BMN 673 in the preoperative period.

IV. To determine the toxicity of daily BMN 673 given preoperatively, with a focus on
postoperative wound healing.

V. To determine feasibility of daily BMN 673 given preoperatively.

OUTLINE:

Patients receive talazoparib orally (PO) once daily (QD) for up to 28 days in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3
months thereafter.

Inclusion Criteria:

- Patients with presumed advanced-stage high grade serous ovarian, fallopian tube, or
primary peritoneal carcinoma, based on the presence of carcinomatosis, and/or elevated
cancer antigen 125 (CA125), and/or ovarian mass(es), or at the discretion of the
treating physician

- Medically able to undergo primary cytoreductive surgery, at least 7 days and up to 28
days after starting study drug, as determined by treating physician

- No prior therapy for high-grade serous ovarian, fallopian tube, or primary peritoneal
carcinoma

- Patients must be able to swallow and tolerate oral medications and not have
gastrointestinal illnesses that would preclude absorption of BMN 673 (e.g.
uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome; ulcerative
disease)

- Absolute neutrophil count >= 1,500/mcL (measured within 28 days prior to entry/
randomization)

- Hemoglobin >= 9 gm/dL (measured within 28 days prior to entry/ randomization)

- Platelets >= 100,000/mcL (measured within 28 days prior to entry/ randomization)

- Total bilirubin =< 1.5 X upper limit of normal (ULN) (measured within 28 days prior to
entry/ randomization)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit
of normal unless the liver is involved with tumor, in that case, ALT/AST must be =< 5
x upper limit of normal (measured within 28 days prior to entry/ randomization)

- Creatinine clearance >= 50 mL/min (assessed by Cockcroft Gault estimation) (measured
within 28 days prior to entry/ randomization)

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 or 1

- Women of child-bearing potential and their partners must agree to use contraception
(hormonal or barrier method of birth control; abstinence) from the time of study entry
until 30 days after the last dose of study medication; women of child-bearing
potential (intact uterus) should have a negative serum pregnancy test; should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately; female patients must have evidence
of non-child-bearing potential by fulfilling one of the following criteria at
screening:

- Post-menopausal defined as aged more than 50 years and amenorrheic for at least
12 consecutive months following cessation of all exogenous hormonal treatments

- Documentation of irreversible surgical sterilization by hysterectomy, bilateral
oophorectomy or bilateral salpingectomy, but not tubal ligation; male partners
should be instructed to use contraception during the study period

- Women must not breast-feed while taking the study medications

- Patients must be able to understand and willing to sign an informed consent

Exclusion Criteria:

- Prior treatment for ovarian, fallopian tube, or primary peritoneal cancer

- Receipt of any other investigational agents or any additional anti-cancer agents

- Significant symptom burden from presumed diagnosis including large volume ascites,
pain requiring narcotic medication, or shortness of breath on exertion

- Myocardial infarction within 6 months before starting therapy, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or unstable
cardiac arrhythmia requiring medication

- As judged by the investigator, any evidence of severe or uncontrolled systemic
diseases (e.g., severe hepatic impairment, interstitial lung disease [bilateral,
diffuse, parenchymal lung disease], uncontrolled chronic renal diseases
[glomerulonephritis, nephritic syndrome, Fanconi syndrome or renal tubular acidosis]),
or current unstable or uncompensated respiratory or cardiac conditions, or
uncontrolled hypertension (blood pressure >= 140/90), active bleeding diatheses or
active infection including hepatitis B, hepatitis C, and human immunodeficiency virus;
screening for chronic conditions is not required

- As judged by the investigator, the patient is unsuitable to participate in the study
and the patient is unlikely to comply with study procedures, restrictions, and
requirements