Inclusion Criteria:

- Age ≥ 18 years

- Karnofsky Performance Status (KPS) ≥60%

- Urothelial carcinoma of the bladder, urethra, ureter or renal pelvis, with histologic
confirmation at MSKCC. Patients with unresected primary tumors may be enrolled as
long as evidence of metastatic disease is also present.

- Patients must have progressive metastatic disease. Progressive disease will be
defined as new or progressive lesions on cross-sectional imaging (RECIST Version
1.1).

- Patients must have been previously treated, as defined by the following:

- Patients must have received treatment with at least one prior cytotoxic
chemotherapy agent but not more than four prior cytotoxic chemotherapy agents
for urothelial carcinoma. Up to four prior chemotherapy agents are allowed,
since conventional chemotherapy ranges from just one drug (e.g., gemcitabine) to
regimens that contain four agents (e.g., M-VAC is a four-drug regimen containing
methotrexate, vinblastine, doxorubicin, and cisplatin).

The prior therapy must have consisted of at least one of the following: cisplatin,
carboplatin, paclitaxel, docetaxel, or gemcitabine.

o The prior cytotoxic agents may have been administered in the perioperative or metastatic
setting and may have been administered sequentially (e.g., first-line treatment followed
by second-line treatment at time of progression) or as part of a single regimen.

- Patients must have at least one site of measurable disease per RECIST 1.1 criteria
that has not been previously irradiated. If the patient has had previous radiation to
the marker lesion(s), there must be evidence of progression since the radiation.

- Pre-treatment tumor tissue available for PI3K/Akt pathway marker analysis: One
paraffin block, frozen curls or 10 freshly-prepared unstained slides from the most
representative single paraffinembedded tumor tissue block should be submitted. Slides
from the primary tumor are preferred. If both the primary and metastatic tumor blocks
are available, 10 slides from each of the sites should be submitted. If tissue from
the primary tumor is not available, a paraffin block or unstained slides from a
metastatic site are acceptable. Fine needle aspirates (FNAs) have insufficient tumor
tissue and are not permitted.

- Life expectancy of ≥ 12 weeks

- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x
109/L,

- Hemoglobin >9 g/dL

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

- Corrected Calcium = (0.8 * (Normal Albumin - Pt's Albumin)) + Serum Ca

- Potassium and magnesium within normal limits

- 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 welldocumented Gilbert syndrome)

- Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min

- INR ≤ 2

- Serum amylase and lipase ≤ ULN

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

- Ability to swallow oral medication

Exclusion Criteria:

- Patients who have received prior treatment with a P13K inhibitor.

- Patients receiving any other investigational therapies.

- Patients with a known hypersensitivity to BKM120 or to its excipients

- Patients with untreated brain metastases are excluded. However, patients may
participate in this trial if > 4 weeks from completion of therapy (radiation and/or
surgery) for CNS metastases, are clinically stable at the time of registration and
are not receiving corticosteroid therapy

- Patients with acute or chronic hepatic or renal disease or pancreatitis

- Patients with the following mood disorders as judged by the Investigator or a
psychiatrist, or as a result of patient's mood assessment questionnaire:

o 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)

- ≥ CTCAE grade 3 anxiety

o Meet the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood
scale, respectively, or select a positive response of "1", "2", or "3" to question
number 9 regarding the potential for suicidal thoughts in the PHQ-9 (independent of
the total score of the PHQ-9)

- Patients with diarrhea ≥ CTCAE grade 2 or other impairment of gastrointestinal (GI)
function or GI disease that may significantly alter the absorption of BKM120 (e.g.,
ulcerative diseases, uncontrolled, nausea, vomiting, malabsorption syndrome, or small
bowel resection)

- Patient has active cardiac disease including any of the following:

Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Grated
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 arrhythmias requiring a pacemaker or not controlled with
medication

- Conduction abnormality requiring a pacemaker

- Valvular disease with document compromise in cardiac function

- Symptomatic pericarditis

- Patients with uncontrolled diabetes mellitus or steroid-induced diabetes
mellitus.

- 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

- Significant symptomatic deterioration of lung function. If clinically indicated,
pulmonary function tests including measures of lung volumes, DLCO, O2 saturation at
rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates

- Patients who have been treated with any hematopoietic 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

- Patients who are currently receiving treatment with any medication that has the
potential 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. Refer to Appendix A for a list of prohibited
QT-prolonging medications.

Patients receiving chronic treatment with steroids or another immunosuppressive agent o
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 stable low dose corticosteroid treatment
(e.g., dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start
of study treatment are eligible.

- Patients who have taken herbal medications and certain fruits 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 include the CYP3A inhibitors Seville
oranges, grapefruit, pummelos, or exotic citrus fruits.

- Patients who are currently 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
Appendix A for a list of moderate to strong inhibitors of CYP3A4 (Please note that
co-treatment with weak inhibitors of CYP3A4 is allowed).

- Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6
weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug or
whose side effects from chemotherapy or targeted anticancer therapy have not
recovered to a grade 1 before starting the trial.

- Patients who have received any continuous or intermittent small molecule therapeutics
(excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study
drug or who have not recovered from side effects of such therapy.

Patients who 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

- Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug,
patients who have not recovered from side effects of any major surgery, or patients
who may require major surgery during the course of the study

- Patients who are currently taking therapeutic doses of warfarin sodium or any other
coumarin-derivative anticoagulant.

Women who are pregnant or breast feeding or adults of child-bearing potential not
employing an effective method of birth control. Women of child-bearing potential, must
have a negative serum pregnancy test ≤ 48 hours prior to initiating treatment. Effective
methods of birth control.

- Known diagnosis of human immunodeficiency virus (HIV) infection

- History of another malignancy within 3 years, except non-melanoma skin cancer,
excised carcinoma in situ of the cervix or adenocarcinoma of the prostate that has
been surgically treated with a post-treatment PSA that is non-detectable

- Patients who are unwilling or unable to abide by the study protocol or cooperate
fully with the investigator