Pazopanib and Everolimus in PI3KCA Mutation Positive/PTEN Loss Patients

Exclusion criteria

• . Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery +/- radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anti-convulsants in prior 2 weeks.
• . Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:Active peptic ulcer disease; Known intraluminal metastatic lesion/s with risk of bleeding; Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease),or other gastrointestinal conditions with increased risk of perforation; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior beginning study treatment.
• . Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to; Malabsorption syndrome; Major resection of the stomach or small bowel
• . Corrected QT (QTc) \> 480 msecs.
• . History of any one or more of the following cardiovascular conditions within the past 6 months:Cerebrovascular accident, Myocardial infarction, Unstable angina , Cardiac angioplasty or stenting, Coronary artery bypass graft surgery, Class III or IV heart failure, as defined by the New York Heart Association (NYHA), Untreated pulmonary embolism (PE) or deep venous thrombosis (DVT). Note: subjects with recent PE or DVT who have been therapeutically coagulated for at least 6 weeks are eligible.
• . Uncontrolled systemic vascular hypertension (systolic blood pressure \>/= 140 mmHg, diastolic blood pressure \>/= 90 mmHg). Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement. These three values should be averaged to obtain the mean diastolic BP and mean systolic BP. The mean SBP/DBP ration must be \< 140/90.
• . Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
• . Evidence of active bleeding or bleeding diathesis.