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

Inclusion Criteria:

Histological or cytological proof of transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis (urothelial carcinoma). Histology may be mixed, but still requires a component of TCC.
Measurable disease according to RECIST and obtained by imaging within 30 days prior to registration for protocol therapy.
Must be ineligible for cisplatin, based on the following, within 30 days prior to registration for protocol therapy.
Prior radiation therapy is allowed to < 25% of the bone marrow.
Written informed consent and HIPAA authorization for release of personal health information.
Age > 18 years at the time of consent.
Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 8 weeks after treatment discontinuation.
Females of childbearing potential must have a negative pregnancy test within 7 days prior to prior to registration for protocol therapy.
Females must not be breastfeeding.

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.