Molecular Features and Pathways in Predicting Drug Resistance in Patients With Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide

Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
* Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to 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 progression defined by a minimum of three rising PSA levels with an interval of \>= 1 week between each determination; the PSA value at screening should be \>= 2 ug/L (2 ng/ml)
  * 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
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Clinically able, in the opinion of the investigator, to receive MDV3100 (enzalutamide)
* Willing and able to give informed consent
* 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

Exclusion Criteria:

* Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
* Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed)
* Platelet count \< 75,000/uL
* Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time PTT \> 1.5 times the institutional upper limit of normal (ULN)
* Structurally unstable bone lesions suggesting impending fracture
* Previous treatment with MDV3100, ARN-509, or BMS-641988
* Medical contraindications to stopping aspirin, Coumadin or other anticoagulants for 1 week prior to image-guided tumor biopsies
* Plans to initiate treatment with an investigational agent while on study prior to discontinuation of MDV3100 treatment
* A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm