Phase II Trial of Atezolizumab in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

-The S1605 Pre-Registration Study Chair Approval Form must be signed by an S1605 Study Chair.
-Histologically proven, recurrent, non-muscle invasive urothelial carcinoma of the bladder within 60 days prior to registration.
-Must be Stage T1 High-Grade, Stage CIS, or Stage Ta High-Grade. (see Section 5.1f for high-grade T1).
-May have a mixed urothelial carcinoma and a glandular and/or squamous component, but not the presence of other histologic variants, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous carcinoma in situ.
-Must have had all visible tumor resected completely within 60 days prior to registration.
-Cis disease is not expected to be completely excised.
-Must have tumor tissue from the histologic diagnosis of recurrence available for central pathology review submission.
-Must have had cystoscopy confirming no visible papillary tumor within 21 days prior to registration, or TURBT or bladder biopsy within 21 days prior to registration.
-Must have had urine cytology within 21 days prior to registration.
-Cytology for patients with CIS component is not expected to be negative for malignant cells.
-If cytology for male patients with only Ta/T1 disease in the absence of CIS is positive for malignant cells, must have had a biopsy of the prostatic urethra within the previous six months.
-All patients with T1 urothelial carcinoma at study entry must undergo re-TURBT within 60 days prior to registration, and must have evidence of uninvolved muscularis propria in the pathologic specimen from either the first or the second TURBT. Tissue from the re-resection must be submitted for central review in addition to the tissue from the first TURBT (see Section 12.0). The TURBT that identified the recurrent T1 disease may have taken place more than 60 days prior to registration but not more than 120 days. Patients with high grade Ta or CIS do not require a re-TURBT, but if this is performed at the discretion of the treating physician, the second TURBT must be within 60 days of registration. There is no requirement for muscularis propria in the specimen of Ta/CIS patients, but the tissue from the first and second TURBTs must be submitted for central review. If a patient with Ta/T1 disease undergoes repeat TURBT, the patient will be stratified as having CIS if there is CIS on either TURBT.
-Patients must not have had urothelial carcinoma in the prostatic urethra within the previous 24 months or muscle invasive urothelial carcinoma of the bladder at any time. Patients with prior urothelial carcinoma in the upper urinary tract within the previous 24 months will only be eligible if they had ≤ T1 carcinoma and were treated with nephroureterectomy. Patients must have a CT or MRI (including CT-IVP, CT-urogram or MR-urogram) of the abdomen and pelvis to rule out upper tract malignancy and intra-abdominal metastases within 90 days prior to registration. If a patient cannot tolerate intravenous contrast, a retrograde pyelogram should be performed within 90 days prior to registration.
-Must be deemed unfit for radical cystectomy or have refused radical cystectomy with clear documentation.
-Must be BCG-unresponsive (see definition in Section 5.3.a).
-Adverse events associated with any prior surgery and intravesical therapy must have resolved to Grade </= 2 prior to registration.
-Must not have had prior systemic chemo for bladder cancer or systemic immunotherapy including but not limited to interferon alfa-2b, high dose IL-2, PEG-IFN, anti-PD-1, anti_PD-L1, intra-tumoral, or vaccine therapies within 6 weeks prior to registration.
-Must not have received or be planning to receive any prohibited therapies listed in Section 7.3 during protocol treatment. Prior intravesical interferon therapy is allowed.
-Must not be planning to receive other anti-cancer therapy while on this protocol.
-Must not have received any prior radiation to the bladder for bladder cancer.
-Must not have received treatment with systemic immunosuppressive medications within 4 weeks prior to registration. (See exceptions in Section 5.2.f.)
-Must not have received a live, attenuated vaccine within 4 weeks before registration or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of study drug. Influenza vaccination should be given during influenza season only (approx. Oct to Mar). Must not receive live, attenuated influenza vaccine within 4 weeks prior to registration or at any time during the study.
-Must not require treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with study drug.
-Must be >/= 18 years of age
-Within 42 days prior to registration: ANC >/= 1,500/mcL; platelets >/= 100,000/mcL; hemoglobin >/= 9 g/dL; total bilirubin </= 1.5 x IULN (except Gilbert�s Syndrome must have <3.0 mg/dL); AST or ALT </= 2 x IULN; serum creatinine </= 1.5 x IULN or measured or calculated creatinine clearance >/= 30 mL/min; baseline ECG.
-Zubrod performance status </= 2.
-No history of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis.
-Must not have an active infection requiring oral or IV antibiotic within 14 days prior to registration. Patients receiving prophylactic antibiotics (e.g., for prevention of UTI or COPD) are eligible.
-Must not have severe infections within 28 days prior to registration.
-Must not have active autoimmune disease that has required systemic treatment in past two years.
-Must not have undergone prior allogeneic bone marrow transplantation or prior solid organ transplantation.
-Must not have active tuberculosis.
-Must not have active hepatitis B (chronic or acute) or active hepatitis C. (Patients with + Hep C antibody with PCR � for HCV RNA are eligible)
-Patients positive for HIV are eligible only if they meet the criteria in Section 5.3.n.
-Must not have prior malignancy except those listed in Section 5.3o.
-Must not be pregnant or nursing.
-Must agree to use adequate contraception prior to study entry, for the duration of the study and for 5 months after the last dose of study drug.
-Must not be known to be allergic to Chinese hamster egg or ovaries.
-Must have available representative slides for central path review.