Dose Finding Study of BKM 120 in Combination With LH-RH Agonists and Bicalutamide in Men With Non Castrate Metastatic Prostate Cancer

Inclusion Criteria: * Signed Informed Consent Form (ICF) prior to screening * Male patients (≥ 18 years) * WHO performance status ≤ 2 * Histologically-confirmed adenocarcinoma of the prostate * Patients with non castrate metastatic prostate cancer, with radiological metastatic disease ; patients with metastatic disease is documented on a Pet-Scan to choline is also eligible * No previous chemotherapy treatment during the metastatic disease * Neoadjuvant or adjuvant androgen deprivation therapy (ADT) treatment or for rising PSA is permitted if the ADT have been stopped for at least one year without metastasis or PSA increase during this time * LH-RH agonists and bicalutamide had to began ≥ 28 days before registration * Minimum pre treatment PSA \> 5 ng/ml * Patient has adequate bone marrow and organ function as defined by the following laboratory values: * Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L * Platelets ≥ 100 x 109/L * Hemoglobin ≥ 9.0 g/dL * INR ≤ 2 * Potassium, calcium, magnesium within normal limits for the institution * Serum Creatinine ≤ 1.5 x ULN * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ≤ 3.0 x ULN if liver metastases are present) * Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome) * Fasting plasma glucose (FPG) ≤ 120 mg/dL or ≤ 6.7 mmol/L 11. Agree to use effective contraception during the study and for at least 16 weeks after discontinuation 12. Patient is able to swallow and retain oral medication Exclusion Criteria: * Patients eligible for this study must not meet any of the following criteria: * Patient has received previous treatment with PI3K and/or mTOR inhibitors * Patient has a concurrent malignancy or has a malignancy within 3 years of study enrollment, (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer) * ADT \> 3 months * Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9): * 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) or patients with active severe personality disorders (defined according to DSM-IV) are not eligible Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug * ≥ CTCAE grade 3 anxiety * Patient is concurrently using other approved or investigational antineoplastic agent Patient has received pelvic and/or para-aortic radiotherapy ≤ 28 days prior to enrollment in this study or has not recovered from side effects of such therapy at the time of initiation of screening procedures Patient has had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery Patient has poorly controlled diabetes mellitus (HbA1c \> 8 %) Patient with uncontrolled hypertension Patient has active cardiac disease including any of the following: * Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) * QTc \> 480 msec on screening ECG (using the QTcF formula * Angina pectoris that requires the use of anti-anginal medication * Ventricular arrhythmias except for benign premature ventricular contractions * Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication * Conduction abnormality requiring a pacemaker * Valvular disease with documented compromise in cardiac function * Symptomatic pericarditis \- Patient has a 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 * Patient is currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug * Patient has 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) * Patient receiving 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., intra-articular) are allowed. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment (e.g., dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment, are eligible * Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate her participation in the clinical study (e.g.,chronic pancreatitis, active chronic hepatitis etc.) * Patient has a history of non-compliance to medical regimen * Patient is currently being treated 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 annex 9 for a list of prohibited CYP3A inhibitors and inducers Note: the oral anti-diabetic drugs troglitazone and pioglitazone are CYP3A inducers * Patient has a known history of HIV (testing not mandatory) infection