Nivolumab and RT in Treating Patients With Localized/Locally Advanced Urothelial Bladder Cancer Ineligible for Chemo
Condition: Stage II Bladder Urothelial Carcinoma AJCC v6 and v7; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage IV Bladder Urothelial Carcinoma AJCC v7
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Nivolumab; Radiation
Intervention description: Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days (2 weeks) for up to 14 courses (6 months) in the absence of disease progression or unacceptable toxicity. Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.; Beginning 3 days of course 1, patients undergo radiation therapy over 32-35 on weeks 1, 3, 5, 7 and 9.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well nivolumab works with radiation therapy in treating
      patients with urothelial bladder cancer that has spread from its original site of growth to
      nearby tissues or lymph nodes and are ineligible for chemotherapy. Monoclonal antibodies,
      such as nivolumab, may interfere with the ability of tumor cells to grow and spread.
      Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving
      nivolumab and radiation therapy may work better in treating patients with urothelial bladder
      cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        - Localized urothelial cancer of bladder with presence of transitional cell carcinoma (TCC)
        component; mixed histologies are allowed Clinical or pathologic stage T2 -T4 disease
        including T4a and 4b if feasible to treat with radiation therapy Locoregional lymph node
        metastases are permitted but patients with distant metastases are ineligible; imaging to
        evaluate for distant metastases should consist of a minimum of computed tomography
        (CT)/magnetic resonance imaging (MRI) of abdomen/pelvis or CT urogram and a chest x-ray
        (CXR) or CT chest; patients for which there is clinical suspicion or symptoms of bone
        metastasis should have a bone scan completed to rule out metastatic disease prior to
        enrollment on study Agreeable to consider radiation therapy (RT) for the urothelial cancer:
        patients have to be evaluated by a radiation oncologist and deemed to be candidates for RT

        The patients must not be candidates for chemotherapy due to at least one of the following
        reasons:

          -  Performance status of 2

          -  Creatinine clearance =< 60 ml/min as calculated by the Cockcroft-Gault formula

          -  Cardiac disease such as New York Heart Association (NYHA) class III or IV heart
             failure or cardiac ischemia within the last 12 months, grade 2 or greater neuropathy,
             or other comorbidities based on which patient is not considered a candidate for
             chemotherapy Alkaline phosphatase =< 3 x upper limit of normal Aspartate
             aminotransferase (AST) =< 3 x upper limit of normal Alanine aminotransferase (ALT) =<
             3 x upper limit of normal Bilirubin < 1.5 x upper limit of normal (ULN) Absolute
             neutrophil count >= 1500/mm^3 Hemoglobin >= 9 g/dL Platelets >= 100 K/mm^3 Performance
             score (PS) of 0-2 by Zubrod score Life expectancy of 12 months Willingness to sign
             informed consent Patients cannot have active autoimmune disease or immunosuppressive
             conditions Serum creatinine =< 1.5 X institutional ULN or creatinine clearance > 40
             ml/min as calculated by the Cockcroft-Gault formula In females with childbearing
             potential, or men with partners of child bearing potential, willingness to use
             adequate contraception for a minimum duration of 155 days in females and 215 days in
             males, after last dose of nivolumab Maximal tumor resection has been performed as
             feasible

        Exclusion Criteria:

        - The subject has received cytotoxic chemotherapy (including investigational cytotoxic
        chemotherapy) or biologic agents (e.g., cytokines or antibodies) for urothelial cancer
        within 4 weeks, or intravesical Bacillus Calmette-Guerin (BCG) within 6 weeks of the first
        dose of study treatment Prior treatment with any PD-1 or PDL-1 inhibitor

        The subject has received therapeutic radiation:

          -  To the bladder/prostate/rectum pelvis

          -  To any other site(s) within 28 days of the first dose of study treatment Obstructive
             renal failure that is not relieved with stents or nephrostomy tube/s The subject has
             received any other type of investigational agent within 28 days before the first dose
             of study treatment Steroid doses greater than an equivalent of prednisone 10 mg daily
             The subject has prothrombin time (PT)/international normalized ratio (INR) or partial
             thromboplastin time (PTT) test results at screening >= 2 x the laboratory ULN
             Uncontrolled hematuria

        The subject has uncontrolled, significant intercurrent or recent illness including, but not
        limited to, the following conditions:

          -  Cardiovascular disorders such as uncontrolled arrhythmias or uncontrolled congestive
             heart failure

          -  Gastrointestinal disorders particularly those associated with a high risk of
             perforation or fistula formation including:

               -  Any of the following at the time of screening

                    -  Active peptic ulcer disease,

                    -  Active inflammatory bowel disease (including ulcerative colitis and Crohn's
                       disease), diverticulitis, cholecystitis, symptomatic cholangitis or
                       appendicitis

               -  Any of the following within 6 months before the first dose of study treatment:

                    -  History of abdominal fistula

                    -  Bowel perforation The subject has a previously identified allergy or
                       hypersensitivity to components of the study treatment formulation The
                       subject is unable or unwilling to abide by the study protocol or cooperate
                       fully with the investigator or designee Presence of another invasive
                       malignancy, which required systemic therapy within 12 months of protocol
                       enrollment, except for resected skin cancers or prostate cancer that is in
                       remission Pregnant or nursing women Patient is a candidate for radical
                       cystectomy as a potentially curative option. The patient may not be a
                       candidate for radical cystectomy due to any of the following reasons:
                       comorbidities, patient preference, or physician discretion. Patients with
                       inherited syndromes associated with hypersensitivity to ionizing radiation
                       (e.g., ataxia-telangiectasia, Nijmegen breakage syndrome)