This is a Phase II study. The purpose of this study is to find out what effects, good and/or bad enzalutamide has on the patient and the cancer. All patients who enter the study will be closely monitored for side-effects. If multiple patients develop significant side effects from enzalutamide, the study may be stopped early.

Enzalutamide is an androgen-receptor inhibitor, which means that it blocks the activity of the hormone testosterone. In ovarian, fallopian tube, and primary peritoneal cancers that express the androgen receptor, blocking the androgen-receptor may possibly slow or stop tumor growth. Enzalutamide has been studied in women with breast cancer, but this is the first study using enzalutamide for the treatment of patients with ovarian, primary peritoneal, or fallopian tube cancer.

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