Neoadjuvant BKM120 in High-risk Prostate Cancer

INCLUSION CRITERIA 1. Histologically confirmed adenocarcinoma of the prostate 2. Candidate for radical prostatectomy 3. Prostate cancer with the following pathological characteristics: 1. Gleason sum \> 8 AND at least 2 discrete core biopsies containing a minimum of 20% cancer or, 2. Gleason pattern 4 + 3 = 7 and greater than 50% of biopsies positive for prostate cancer 4. Age \>= 18 years 5. Eastern Cooperative Oncology Group (ECOG) performance status \> 2 6. Ability to take oral medications (capsule must be swallowed with liquid) 7. Adequate bone marrow function as shown by: Absolute Neutrophil Count (ANC) \>= 1.5 x 109/liter, Platelets ≥ 100 x 109/L, Hemoglobin \> 9 grams(g) /decilitre(dL) 8. Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed) 9. Magnesium \>= the lower limit of normal 10. Potassium within normal limits for the institution 11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range 12. Serum bilirubin within normal range (or total bilirubin \<= 3.0 x upper limit of normal (ULN) with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) 13. Serum creatinine \<= 1.5 x upper limit of normal (ULN) or 24-hour clearance \>= 50 milliliter per min (mL/min) 14. Serum amylase \<= ULN 15. Serum lipase \<= ULN 16. Fasting plasma glucose \<= 120 mg/dL (6.7 mmol/L) 17. International Normalized Ratio (INR) \<= 2 18. Men of reproductive potential and their female partners must use highly effective contraception during treatment, for 5 half-lives (8 days) after stopping treatment and for additional 12 weeks (3 months in total after study drug discontinuation) and should not father a child in this period The highly effective contraception is defined as either: 1. True abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 2. Sterilization: Female partners have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. 3. Male participant sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). 4. Use of a combination of any two of the following (a+b): 5. Female partner with prior placement of an intrauterine device (IUD) or intrauterine system (IUS) 6. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository • Oral contraception use by female partners, injected or implanted hormonal methods are not allowed as BKM120 potentially decreases the effectiveness of hormonal contraceptives. * Fertile males, defined as all males physiologically capable of conceiving offspring must use condom during treatment, for 5 half-lives (8 days) after stopping treatment and for additional 12 weeks (3 months in total after study drug discontinuation) and should not father a child in this period. 19. Ability to understand and the willingness to sign a written informed consent document EXCLUSION CRITERIA 1. Prior treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor 2. Known hypersensitivity to BKM120 or to its excipients 3. History of another malignancy within 3 years, except cured basal cell carcinoma of the skin 4. Hormonal therapy with Gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists or high dose bicalutamide within 1 month of enrollment unless serum testosterone is within normal limits. 5. Following mood disorders as judged by the investigator and/or symptom management service co-investigator, or as a result of patient's mood assessment questionnaire: • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) • Current \>= NCI Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety • Meets the cut-off score of \>= 10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of \>= 15 in the Generalized Anxiety Disorder (GAD-7) mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study 6. Current diarrhea \>= CTCAE grade 2 7. Active cardiac disease including any of the following: • History of left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO) • QTc \> 450 msec on screening electrocardiogram (ECG (using the QTcF formula) * Angina pectoris that requires the use of anti-anginal medication * History of ventricular arrhythmias except for benign premature ventricular contractions * Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication * Conduction abnormality requiring a pacemaker * Valvular disease with documented compromise in cardiac function * Symptomatic pericarditis 8. History of cardiac dysfunction including any of the following: * Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Documented cardiomyopathy 9. Poorly controlled diabetes mellitus or active, steroid-induced diabetes mellitus 10. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol 11. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with unresolved diarrhea will be excluded as previously indicated 12. Treatment with any hematopoietic colony-stimulating growth factors (G-CSF or GM-CSF) \<= 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued 13. Current treatment with medication with a known risk to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug. Please refer to section 10.2 for a list of prohibited QT prolonging drugs with risk of Torsades de Pointes. 14. Current, chronic treatment with steroids or another immunosuppressive agent • Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intr-articular) are allowed. If a patient stops corticosteroids prior to study participation, a 2-week washout is required. 15. Taking herbal medications and certain fruits and juices within 7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits and juice include the Cytochrome P450 3A (CYP3A) inhibitors: Seville oranges, grapefruit, and pomelos. 16. Current treatment with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Section 10.2 for a list of prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak inhibitors of CYP3A is allowed) 17. Chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug 18. Any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) \<= 5 effective half lives prior to starting study drug or patients who have not recovered from side effects of such therapy 19 Major surgery \<= 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy 20\. Current treatment with warfarin sodium or any other coumadin-derivative anticoagulant 21. Known diagnosis of human immunodeficiency virus (HIV) infection. Testing is not required for participation. 22\. Unable or unwilling to abide by the study protocol or cooperate fully with the investigator