First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma

Exclusion Criteria

• •No prior chemotherapy for metastatic disease. Prior chemotherapy in the neoadjuvant/adjuvant setting is allowed if completed at least 12 months prior to registration for protocol therapy.
• •No active CNS metastases or leptomeningeal metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis.
• •No prior malignancy is allowed except for adequately treated basal cell or adequately treated squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 7 prostate cancers (treated definitively with no evidence of PSA progression), or other cancer for which the patient has been disease-free for at least 5 years.
• •No treatment with any anticancer therapy or investigational agent within 30 days prior to registration for protocol therapy.
• •No known hypersensitivity to any protocol treatment.
• •No prior treatment with mTOR inhibitor (sirolimus, temsirolimus, everolimus).
• •No history of immunization with attenuated live vaccines within one week prior to registration for protocol therapy or during study period.
• •No severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air.
• •No uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN.
• •No active (acute or chronic) or uncontrolled severe infections.
• •No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis.
• •No known history of HIV seropositivity.
• •No impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
• •No active, bleeding diathesis.
• •No history of major surgery (defined as requiring general anesthesia) or significant traumatic injury within 30 days prior to registration for protocol therapy.