Enzalutamide in Patients With Androgen Receptor Positive (AR+) Ovarian, Primary Peritoneal or Fallopian Tube Cancer and One, Two or Three Prior Therapies

Inclusion Criteria:

- Advanced or recurrent epithelial ovarian, fallopian tube or primary peritoneal
carcinoma. Histologic documentation of the original primary tumor is required via the
pathology report

- AR expression ≥5% by IHC. In cases where multiple blocks are available staining will
be performed on unstained slides from 3 separate blocks. If ≥ 5% AR tumor staining is
seen on ≥ 1 slide the tumor will be considered to be AR+.

- Patients with the following histologic cell types are eligible: serous adenocarcinoma,
endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma,
clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell
carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified

- Measurable disease as defined by RECIST 1.1. Measurable disease is defined as at least
one lesion that can be accurately measured in at least one dimension. Each lesion must
be ≥10mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20mm
when measured by chest x-ray. Lymph nodes must be ≥ 15mm in short axis when measured
by CT or MRI

- Patients must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease

- Patients may have received, but are not required to have received, one or two
additional cytotoxic regimens for management of recurrent or persistent disease

- Patients who have received only one prior cytotoxic regimen (platinum-based regimen
management of primary disease), must have a platinum-free interval of less than 12
months, or have progressed during platinum-based therapy, or have persistent disease
after a platinum-based therapy

- Patients are allowed to receive, but are not required to receive, non-cytotoxic
therapy (such as bevacizumab) as part of their primary treatment regimen.

- Patients are allowed to receive, but are not required to receive, non-cytotoxic
therapy for management of recurrent or persistent disease

- Must be ≥ 18 years of age

- Karnofsky Performance Status (KPS) of ≥ 70%

- Life expectancy of ≥ 12 weeks Women of child-bearing potential must have a negative
pregnancy test within 14 days prior to commencement of study treatment

- Women of child bearing potential must use an effective form of contraception during
study and for at least 6 months after completion of study treatment

- Recovery from effects of recent surgery, radiotherapy, or chemotherapy

- At least 4 weeks out from their last dose of radiation therapy

- At least 4 weeks post-op from any major surgical procedure

- At least 3 weeks out from their last dose of chemotherapy and/or
biologic/targeted therapy

- No prior hormonal therapy for treatment of cancer within the past 21 days

- Absence of any psychological, familial, sociological or geographic condition that
would potentially hamper compliance with the study protocol

- Prior use of or participation in a clinical trial evaluating and agent that either
blocks androgen synthesis (e.g. abiraterone acetate, TAK-700, TAK-683, TAK-448) or
targets the AR (e.g., bicalutamide, BMS-641988) (patients who are known to have only
received placebo in these studies are eligible)

- Laboratory Test Findings performed within 14 days prior to initiation of study drug
showing:

Bone marrow function:

Absolute neutrophil count (ANC) ≥ 1,000/mcL Platelets ≥ 100,000/mcL Hemoglobin ≥ 8 g/dL o
Renal function: Creatinine ≤ 1.5 x ULN

o Hepatic function: Bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN

- Resolution of all acute toxic effects of prior therapy to NCI CTCAE (Version 4.0)
Grade ≤ 1, with the exception of unresolved Grade 2 neuropathy and Grade 2 alopecia,
which are allowed

- Patients must be able to swallow tablets whole, without crushing

Exclusion Criteria:

- A history of another invasive malignancy (other than non-melanoma skin cancer or
curatively treated in situ carcinoma) with evidence of disease within the past 3 years

- Use of a medication known to lower the seizure threshold within 28 days of first dose
of study drug

- Known brain metastasis

- History of seizure

- Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95mmHg) despite
medical treatment. Patients with a history of hypertension are allowed provided blood
pressure is controlled by anti-hypertensive treatment.

- Clinically significant heart disease as evidenced by myocardial infarction or arterial
thrombotic event within the past 6 months, severe or unstable angina, or New York
Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction
measurement of < 50% at baseline

- Refractory nausea and vomiting, requirement for parenteral hydration and/or nutrition,
drainage gastrostomy tube, malabsorption, external biliary shunt, or significant small
bowel resection that would preclude adequate study drug absorption

- Anticipated or ongoing administration of anti-cancer therapies other than those
administered in this study