Cisplatin, Etoposide and PI3K Inhibitor BKM120 in Treating Patients With Advanced Solid Tumors or Small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of combining BKM120 (PI3K inhibitor BKM120) with
cisplatin and etoposide in advanced solid tumors, with emphasis on small cell lung cancer
(SCLC).

SECONDARY OBJECTIVE:

I. To determine the MTD (maximally tolerated dose) of BKM120 in combination with
cisplatin/etoposide.

II. To describe the dose limiting toxicities (DLT) and toxicity profile associated with
BKM120 in combination with cisplatin/etoposide.

III. To determine the preliminary efficacy of BKM120 in combination with cisplatin/etoposide
in an expanded cohort of patients with SCLC.

IV. To characterize the pharmacokinetic (PK) parameters of BKM120 in this combination.

V. To collect blood samples for future exploratory biomarker analysis.

OUTLINE: This is a dose-escalation study of PI3K inhibitor BKM120.

Patients receive PI3K Inhibitor BKM120 orally (PO) once daily (QD) on days 1-21, cisplatin
intravenously (IV) over 2 hours on day 1 and etoposide IV over 1 hour on days 1-3. Treatment
repeats every 21 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity.

After completion of treatment, patients are followed for 30 days.

Inclusion Criteria:

- Histological or cytological proven advanced solid tumors

- =< 3 chemotherapy regimens for metastatic disease; any number of prior targeted or
biologic therapies is allowed; (in the expansion cohort, patients must be chemo naïve)

- ECOG performance status =< 2

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Hemoglobin (Hb) > 9 g/dL

- Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use
for malignant hypercalcemia control is not allowed)

- Magnesium >= the lower limit of normal

- Potassium within normal limits for the institution

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal
range (or =< 3.0 x upper limit of normal (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)

- Serum creatinine =< 1.5 x ULN or calculated clearance >= 60 mL/min

- Serum albumin >= 3 g/dl

- Serum amylase =< ULN

- Serum lipase =< ULN

- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)

- International normalized ratio (INR) =< 2

- Ability to swallow pills

- Negative serum pregnancy test

Exclusion Criteria:

- Received prior treatment with a P13K inhibitor

- Received > 300 mg/m^2 of cisplatin and/or for whom cisplatin would not be beneficial

- Prior treatment with any investigational drug within the preceding 3 weeks

- Known hypersensitivity to BKM120 or to its excipients

- Untreated brain metastases are excluded

- Acute or chronic liver, renal disease or pancreatitis

- Following mood disorders as judged by the Investigator or a psychiatrist, or as a
result of patient's mood assessment questionnaire

- Diarrhea >= CTCAE grade 2

- Active cardiac disease

- History of cardiac dysfunction

- Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus

- Other concurrent severe and/or uncontrolled concomitant medical conditions

- 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

- Treated with any hematopoietic colony-stimulating growth factors

- Currently receiving 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

- Chronic treatment with steroids or another immunosuppressive agent

- Herbal medications and certain fruits within 7 days prior to starting study drug

- 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

- Intravenous chemotherapy or targeted anticancer therapy =< 4 weeks

- Any continuous or intermittent oral small molecule therapeutics

- 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

- Undergone major surgery =< 2 weeks prior to starting study drug or who have not
recovered from side effects of such therapy

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

- Women who are pregnant or breast feeding or adults of reproductive potential not
employing an effective method of birth control

- Known diagnosis of HIV infection

- History of another active malignancy

- Unable or unwilling to abide by the study protocol or cooperate fully with the
investigator treatments