First-line Everolimus +/- Paclitaxel for Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma
Condition: Transitional Cell Carcinoma; Bladder Carcinoma; Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms
Intervention: Everolimus; Everolimus; Paclitaxel
Intervention description: 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.; 10 mg PO daily (continuously, without scheduled treatment interruptions). The cycle length will last 28 days. Everolimus will be dispensed on Day 1 of each cycle by the study center personnel on an outpatient basis.; Paclitaxel 80 mg/m2 IV as a 1 hour infusion on days 1, 8, and 15, of a 28-day cycle.
Intervention MeSH terms: Paclitaxel; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this trial is to explore the activity and safety of everolimus +/- paclitaxel
      as first-line therapy for cisplatin-ineligible patients with advanced urothelial carcinoma.
    

Eligibility criteria:

        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.