Patient description: The patient is a 57-year-old man with abdominal pain and vomiting. The pain started gradually about 20 hours ago in the epigastric and periumbilical regions, radiating to his back. He drinks around 60 units of alcohol per week and smokes 22 cigarettes per day. He is healthy with no history of allergies or using any medications. His family history is positive for type 2 diabetes (his father and sister). He lives alone and has no children. The abdomen is tender and soft. His bowel sounds are normal. His heart rate is 115/min and blood pressure 110/75 mmHg. The lab results are remarkable for leukocytosis (19.5), urea of 8.5, high CRP (145), high amylase (1200) and Glc level of 15. Cross-sectional imaging was negative for obstructive pancreatitis.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Metastatic Transitional Cell Carcinoma of the Urothelium 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 1.1 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 Patients enrolling in the Phase II study must have 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 Patients enrolling in the Expansion Cohort must have prior mutational testing demonstrating alterations within the PI3K/Akt/mTOR pathway predicted to result in pathway activation Life expectancy of ≥ 12 weeks  Patients who have received prior treatment with a P13K inhibitor Patients receiving any other investigational therapies Patients with a known hypersensitivity to Buparlisib 120 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 Buparlisib120 (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)