BKM120 in Metastatic Castration-resistant Prostate Cancer

This is an open label, single arm phase II study of BKM120 in men with metastatic castration
resistant prostate cancer (CRPC) who have progressed on or following completion of
docetaxel-based chemotherapy. Prior progression on cabazitaxel, provenge, abiraterone, or
enzalutamide (MDV3100) is also permitted. Patients must have baseline evaluations performed
prior to the first dose of study drug and must meet all inclusion and exclusion criteria.
Results of the baseline evaluations, which assure that all inclusion and exclusion criteria
have been satisfied, must be reviewed by the Principal Investigator or his/her designee
prior to enrollment of that patient. In addition, the patient must be thoroughly informed
about all aspects of the study, including the study visit schedule and required evaluations
and all regulatory requirements for informed consent. The written informed consent must be
obtained from the patient prior to protocol-specific screening tests. The following criteria
apply to all patients enrolled onto the study unless otherwise specified.

Inclusion Criteria:

- Age ≥ 18 years

- Karnofsky performance status ≥ 70

- Life expectancy of ≥ 12 weeks as determined by treating investigator

- Adequate laboratory parameters

- Histologically confirmed diagnosis of adenocarcinoma of the prostate. Histologic
variants of prostate cancer, including neuroendocrine features and small cell
carcinoma of the prostate are permitted

- Radiographic evidence of metastatic disease

- Evidence of disease progression on androgen deprivation therapy (ADT)

- A minimum of 4 weeks elapsed off of antiandrogen therapy prior to registration (i.e.
flutamide, nilutamide) and 6 weeks for bicalutamide, without evidence of an
anti-androgen withdrawal response. Patients who did not have a PSA decline with the
most recent antiandrogen therapy require only a 2 week washout period prior to
registration

- A minimum of 2 weeks from prior abiraterone acetate, sipuleucel-T, MDV3100, orteronel
(TAK700), ketoconazole, or other experimental anti-cancer therapies prior to
registration is required. Concomitant treatment with enzalutamide is permitted.

- At least one prior systemic chemotherapy regimen FDA approved for metastatic prostate
cancer

- A minimum of 4 weeks from any major surgery prior to registration

Exclusion Criteria:

- Have received prior treatment with a PI3K inhibitor

- Known hypersensitivity to BKM120 or to its excipients

- Untreated brain metastases

- Patients with hepatitis B or C, other acute or chronic liver disease, or a recent
(within 12 months of administration of first dose of study drug) history of
pancreatitis

- Patients with certain mood disorders as judged by the investigator or a psychiatrist

- History of treatment in an inpatient psychiatric setting

- Concurrent severe and/or uncontrolled cardiac conditions which could compromise
participation in the study

- Other concurrent severe and/or uncontrolled concomitant medical conditions that could
cause unacceptable safety risks or compromise compliance with the protocol

- Uncontrolled diabetes mellitus defined as a fasting plasma glucose level of >120.

- Diarrhea ≥ CTCAE grade 2

- Drugs or substances known to be strong inhibitors or inducers of the isoenzyme CYP3A4
should be avoided as systemic therapy in association with BKM120 as these can alter
its metabolism. Topical use of creams or other applications not absorbed into the
circulation is permitted

- 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)

- Have been treated with any granulocyte colony-stimulating growth factors (e.g.,
G-CSF, 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

- Currently receiving treatment with medication that has the potential to significantly
prolong the QT interval or induce Torsades de Pointes, and the treatment cannot
either be discontinued or switched to a different medication prior to starting study
drug

- Have received immunosuppressive therapy including corticosteroids ≤ 2 weeks prior to
starting study drug. Prednisone at a total daily dose of 10 mg orally or its
equivalent is permitted, if initiated at least 2 weeks prior to enrollment

- History of solid organ or stem cell transplantation

- Have received wide field radiotherapy ≤ 4 weeks or limited field radiation for
palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side
effects of such therapy prior to administration of first dose of study drug

- Have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not
recovered from side effects of such therapy prior to administration of first dose of
study drug

- Currently taking therapeutic doses of warfarin sodium or any other
coumadin-derivative anticoagulant

- Known diagnosis of human immunodeficiency virus (HIV) infection

- History of another malignancy within 3 years, except cured basal cell or squamous
cell carcinoma of the skin or low grade papillary bladder cancer Other inclusion and
exclusion criteria apply