First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma
Condition: Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Gemcitabine; Cisplatin; Ipilimumab
Intervention description: Gemcitabine 1000 mg/m2 Days 1 & 8 (all cycles); Cisplatin 70 mg/m2 Day 1 (all cycles); Ipilimumab 10 mg/kg Day 1 (start cycle 3)
Intervention MeSH terms: Gemcitabine; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Gemcitabine plus cisplatin is standard treatment for advanced urothelial cancer. Ipilimumab
      has shown intriguing activity as neoadjuvant therapy in patients with clinically localized
      bladder cancer undergoing radical cystectomy. The combination of gemcitabine, cisplatin, plus
      ipilimumab may build on the chemosensitivity of urothelial carcinoma to produce more durable
      responses and improved outcomes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological proof of urothelial carcinoma of the urethra, bladder,
             ureters, or renal pelvis.

          -  Advanced (clinical stage T4b, unresectable) or metastatic disease.

          -  Prior radiation therapy is allowed to < 25% of the bone marrow.

          -  Age > 18 years at the time of consent.

          -  Written informed consent and HIPAA authorization for release of personal health
             information.

          -  Females must not be pregnant or breastfeeding.

          -  WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
             or equivalent units of HCG) within 72 hours before the start of ipilimumab.

          -  Men of fathering potential must be using an adequate method of contraception to avoid
             conception throughout the study [and for up to 26 weeks after the last dose of
             investigational product] in such a manner that the risk of pregnancy is minimized.

          -  Prior Autoimmune disease: Patients with a history of inflammatory bowel disease,
             including ulcerative colitis and Crohn's Disease, are excluded from this study, as are
             patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic
             progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
             vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune
             origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). Patients with other
             immune disorders should not be enrolled without discussion with the principal
             investigator.

        Exclusion Criteria:

          -  No active CNS metastases. Subjects with neurological symptoms must undergo a head CT
             scan or brain MRI to exclude brain metastasis.

          -  No prior malignancy is allowed except for cancers that have been definitively treated
             with a risk of recurrence of < 30% based on the treating oncologists assessment.

          -  Patients may not have received prior systemic chemotherapy for metastatic/advanced
             urothelial carcinoma. Prior neoadjuvant/adjuvant therapy is permitted if completed ≥
             12 months prior to registration for protocol therapy. Prior intravesical therapy is
             permitted.

          -  No treatment with any investigational agent within 30 days prior to registration for
             protocol therapy.

          -  No underlying medical or psychiatric condition, which in the opinion of the
             investigator will make the administration of ipilimumab hazardous or obscure the
             interpretation of AEs, such as a condition associated with frequent diarrhea.

          -  No non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             1 month before or after any dose of ipilimumab).

          -  No history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4
             inhibitor or agonist.

          -  No known active or chronic infection with HIV, Hepatitis B, or Hepatitis C.

          -  No clinically significant infections as judged by the treating investigator.

          -  No chronic systemic corticosteroids (defined as the equivalent of prednisone ≥ 20 mg
             PO daily for > 6 months during the past year)