Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

Inclusion Criteria: * Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma; patients without histologically confirmed adenocarcinoma may be eligible if both the treating physician and the study principal investigator (PI) agree that the patient's history is unambiguously indicative of advanced adenocarcinoma * Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); patients who have not had an orchiectomy must maintain effective GnRH-analogue therapy for the duration of the trial * Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy * Willingness to undergo a tumor biopsy at baseline and at disease progression * Serum testosterone level \< 50 ng/dL at screening * Progressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria: * PSA evidence for progressive prostate cancer which consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 1 week apart; if the confirmatory PSA value is less than the screening value, then an additional PSA value greater than #2 will be required to document progression of \>= 1 week * PSA values to be obtained \>= 1 week apart * Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Bone disease progression defined by two or more new lesions on bone scan * Patient's physician has already recommended enzalutamide for treatment of progression * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Willing and able to give informed consent * Estimated life expectancy \>= 6 months * Subjects who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last study drug administration * A minimum of 4 weeks elapsed off of anti-androgen therapy prior to enrollment for flutamide and 6 weeks for bicalutamide and nilutamide without evidence of an anti-androgen withdrawal response; patients who NEVER HAD A PSA decline with the most recent anti-androgen therapy or in whom the response to the most recent anti-androgen was for \< 3 months require only a 2 week washout period prior to first dose of study drug * A minimum of 4 weeks from prior systemic anti-cancer therapies or 3 weeks for radiation treatment prior to enrollment is required Exclusion Criteria: * Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment * Previous treatment with docetaxel for metastatic prostate cancer * Known metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed) * Absolute neutrophil count \< 1,000/uL * Platelet count \< 75,000/uL * Hemoglobin \< 9 g/dL at the screening visit; (NOTE: subject may not have received any growth factors or blood transfusions within seven days of the hematologic laboratory values obtained at the screening visit) * Total bilirubin (TBL) \> 2.5 times the upper limit of normal at the screening visit * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal at the screening visit * Creatinine (Cr) \> 2 mg/dL at the screening visit * Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time (PTT) \> 1.5 times the upper limit of normal * Previous treatment with an agent that blocks adrenal androgen synthesis (e.g. abiraterone acetate, TAK-700, TOK-001, ketoconazole) or second generation androgen receptor (AR) antagonists (e.g., BMS 641988, ARN-509,TOK-001) * Systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of study drug administration are prohibited * Structurally unstable bone lesions suggesting impending fracture * Previous treatment with enzalutamide (MDV3100) * Medical contraindications to stopping aspirin, Coumadin or other anticoagulants prior to image-guided tumor biopsies; follow institutional guidelines when determining drugs to avoid and length of washout * Plans to initiate treatment with an investigational agent during the study * History of seizure or condition that may predispose to seizure; also, history of loss of consciousness or transient ischemic attack within 12 months of (day 1 visit) * Concomitant use of the strong CYP2C8 inhibitors gemfibrozil or trimethoprim (Bactrim) * History of known malabsorption syndrome or prior surgery(ies) that may lead to malabsorption * Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) within 4 weeks of study drug administration (day 1) * Use of the following drugs within 4 weeks of study drug administration: 5 alpha-reductase inhibitors (finasteride, dutasteride), estrogens, Cyproterone acetate, biologic, or other agents with anti-tumor activity against prostate cancer, and androgens (testosterone, dihydroepiandrosterone \[DHEA\], etc.) * A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm