['prostate cancer']
['enzalutamide', 'metformin hydrochloride']

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed prostate cancer with a
             Gleason score available or interpretable; patients must have prostate cancer deemed to
             be castration-resistant by one or more of the following criteria (despite androgen
             deprivation and anti-androgen withdrawal when applicable):

               -  Progression of unidimensionally measurable disease assessed within 28 days prior
                  to initial administration of drug

               -  Progression of evaluable but not measurable disease assessed within 28 days prior
                  to initial administration of drug for PSA evaluation and within 42 days for
                  imaging studies (e.g, bone scans)

               -  NOTE: rising PSA, defined as at least two consecutive rises in PSA to be
                  documented over a reference value (measure 1); the first rising PSA (measure 2)
                  should be taken at least 7 days after the reference value; a third confirmatory
                  PSA measure (2nd beyond the reference level) should be greater than the second
                  measure, and it must be obtained at least 7 days after the 2nd measure; if this
                  is not the case, a fourth PSA is required to be taken and be greater than the
                  second measure; measurable disease is not required

          -  Patients who have measurable disease must have had X-rays, scans or physical
             examinations used for tumor measurement completed within 28 days prior to initial
             administration of drug

          -  Patients must have non-measurable disease (such as nuclear medicine bone scans) and
             non-target lesions (such as PSA level) assessed within 28 days prior to initial
             administration of drug

          -  Soft tissue disease that has been radiated within the two months prior to registration
             is not assessable as measurable disease; soft tissue disease that has been radiated
             two or more months prior to registration is assessable as measurable disease provided
             that the lesion has progressed following radiation; patients must have at least one
             measurable lesion outside the previously irradiated region in order to be considered
             to have measurable disease

          -  Patients must have been surgically or medically castrated; if the method of castration
             was luteinizing hormone-releasing hormone (LHRH) agonists (leuprolide or goserelin),
             then the patient must be willing to continue the use of LHRH agonists; serum
             testosterone must be at castrate levels (< 50 ng/dL) at least 14 days prior to
             registration

          -  If the patient has been treated with non-steroidal anti-androgens (flutamide,
             bicalutamide or nilutamide) or other hormonal treatment (such as ketoconazole), these
             agents must have been stopped at least 28 days prior to enrollment for flutamide or
             ketoconazole, and at least 42 days prior to enrollment for bicalutamide or nilutamide;
             and the patients must have demonstrated progression of disease since the agents were
             suspended

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 60
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Concurrent bisphosphonate or receptor activator of nuclear factor kappa-B
             (RANK)-ligand directed therapy for prevention of skeletal related events or treatment
             of osteoporosis is allowed

          -  Male patient and his female partner who is of childbearing potential must use 2
             acceptable methods of birth control (one of which must include a condom as a barrier
             method of contraception) starting at screening and continuing throughout the study
             period and for 3 months after final study drug administration; two acceptable methods
             of birth control thus include the following: condom (barrier method of contraception)
             AND one of the following is required:

               -  Established use of oral, or injected or implanted hormonal method of
                  contraception by the female partner

               -  Placement of an intrauterine device (IUD) or intrauterine system (IUS) by the
                  female partner

               -  Additional barrier method: occlusive cap (diaphragm or cervical/vault caps) with
                  spermicidal foam/gel film/cream/suppository by the female partner

               -  Tubal ligation in the female partner

               -  Vasectomy or other procedure resulting in infertility (e.g., bilateral
                  orchiectomy), for more than 6 months

          -  Able to swallow the study drug and comply with study requirements

          -  Estimated life expectancy >= 6 months

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had radiotherapy within 2 weeks prior to entering the study or those
             who have not recovered from adverse events due to agents administered more than 4
             weeks earlier

          -  Patients with prior history of seizure, underlying brain injury with loss of
             consciousness, transient ischemic attack within the past 12 months, cerebral vascular
             accident, brain arteriovenous malformation or the use of concomitant medications that
             may lower the seizure threshold or other conditions predisposing to seizure

          -  Patients who are receiving any other investigational agents

          -  Patients who are currently taking metformin; prior metformin use is allowed if last
             dose was 3 months previous to this trial

          -  Patients with diabetes on a different agent or patients with rheumatoid arthritis
             taking hydroxychloroquine (Plaquenil)

          -  Greater than 2 prior therapies in metastatic CRPC (including single-agent docetaxel,
             abiraterone); abiraterone can only be taken pre-chemotherapy

          -  Prior cabazitaxel or radium 233 for prostate cancer

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to enzalutamide or metformin

          -  Participation in a previous clinical trial of enzalutamide or an investigational agent
             that inhibits the androgen receptor (ARN-509) or androgen synthesis

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Patients on antipsychotic medication

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible
      