A Multicenter Phase I/II Trial of Abiraterone Acetate + BEZ235 in Metastatic, Castration-Resistant Prostate Cancer

Inclusion Criteria: Patients eligible for inclusion in this study have to meet all of the following criteria: 1. Patient has provided a signed study Informed Consent Form prior to any screening procedure. 2. Patient is ≥ 18 years of age on the day of consenting to the study. 3. Patients must have histologically confirmed adenocarcinoma of the prostate. 4. Radiographic evidence of disease (bone scan, CT scan, ultrasound or MRI acceptable) that is amenable to image-guided biopsy must be present. 5. Patients must have castrate levels of testosterone (\< 50 ng/dL) on GnRH analogues or have had prior orchiectomy. GnRH analogues must be continued while on study. 6. Progressive disease as demonstrated by a rising PSA or radiographic progression per PCWG2 criteria. 7. Asymptomatic or minimally symptomatic disease: No use of opiate analgesics (EXCLUDING codeine or dextromethorphan) for cancer related pain within 28 days of day 1, cycle 1. 8. Phase II Cohort 1: No prior Abiraterone Acetate therapy 9. Phase II Cohort 2: Immediate prior Abiraterone Acetate therapy is required. No intervening therapy is allowed between Abiraterone Acetate therapy and study therapy. 10. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 11. Men of reproductive potential who have not had a radical prostatectomy must agree to use an effective contraceptive method. Patients who have had a prostatectomy are sterile and do not need to use contraception. 12. Patient has adequate bone marrow and organ function as shown by: * Absolute neutrophil count (ANC) ≥ 1.0 x 109/L * Platelets ≥ 100 x 109/L * Hemoglobin (Hgb) ≥ 9.0 g/dL * INR ≤ 2 * Serum creatinine ≤ 1.5 x ULN * Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN) * AST and ALT ≤ 3 x ULN (or ≤ 5.0 x ULN if hepatic metastases are present) * Fasting plasma glucose (FPG) ≤ 140mg/dL \[7.8 mmol/L\] * HgbA1c ≤8% (Patients with diabetes mellitus not actively being treated and patients with an HgbA1c level between 7-8% will be required to have home glucose monitoring three times weekly during the first cycle. Patients may also be referred to a diabetes specialist as indicated.) Exclusion Criteria: Patients eligible for this study must not meet any of the following criteria: 1. Patient has received previous treatment with PI3K and/or mTOR inhibitors. 2. Phase II Cohort 1: Prior Abiraterone Acetate therapy is an exclusion 3. Prior therapy with any of the following for \>1 month: MDV-3100, Orteronel, ketoconazole or other drugs given with the intention to inhibit CYP 17. 4. Patient has active uncontrolled or symptomatic CNS metastases. Note: A patient with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases \> 90 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases. 5. Patient has a concurrent malignancy or has had a malignancy in the last 3 years prior to start of study treatment (with the exception of adequately treated basal or squamous cell carcinoma or cervical carcinoma in situ). 6. Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug or has not recovered from side effects of such therapy. 7. Patient has had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery. 8. 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) * QTcF \> 480 msec on screening ECG * Unstable angina pectoris * 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 9. 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 10. Family history of congenital long or short QT, or known history of QT/QTc prolongation or Torsades de Pointes (TdP). 11. Patient with medically documented history of active major depressive episodes, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation. 12. Active or uncontrolled infection of hepatitis B or hepatitis C. 13. Inadequately controlled hypertension (i.e., SBP \> 180 mmHg or DBP \> 100 mmHg). 14. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BEZ235 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea grade ≥ 2, malabsorption syndrome or small bowel resection). 15. Use of any chemotherapy, investigational agents, immunotherapy, or hormonal therapy other LHRH agonists within 28 days of the start of treatment on protocol. Use of bone targeted agents including bisphosphanates and RANK ligand inhibitors is allowed if on stable dose; Xgeva or Zometa cannot be started within 28 days of initiating study therapy. 16. Systemic corticosteroids except as part of on label treatment prostate cancer regimens. Note: Topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular) are allowed. 17. Patient is undergoing active treatment for diabetes mellitus. 18. Patient is being treated at start of study treatment with any of the following drugs: * Drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A4 including herbal medications (see Appendix 1 for a list of prohibited CYP3A4 inhibitors and inducers) * Drugs with a known risk to induce Torsades de Pointes (see Appendix 3 for a list of prohibited drugs) * Warfarin and coumadin analogues 19. Patient is consuming Seville oranges, grapefruit, grapefruit hybrids, pomelos and exotic citrus fruits (as well as their juices) during the last 7 days prior to start of treatment. Regular orange juice is permitted. 20. Immunocompromised patients, including known seropositivity for HIV (testing is not mandatory). 21. Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate his participation in the clinical study (e.g. uncontrolled diabetes, chronic pancreatitis, active chronic hepatitis etc.). 22. Patient is not able to understand or to comply with study instructions and requirements or has a history of non-compliance to medical regimen. 23. Patients in whom, in the opinion of the treating physician, should receive cytotoxic chemotherapy with docetaxel.