Phase II Trial of Everolimus or Everolimus Plus Paclitaxel as First-line Therapy in Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma: Hoosier Oncology Group GU10-147

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.