S1806 Phase III Randomized Trial of Concurrent Chemoradiotherapy with or Without Atezolizumab in Localized Muscle Invasive Bladder Cancer
Johns Hopkins Kimmel Cancer Center in Baltimore
This phase III trial studies how well chemotherapy and radiation therapy work with or without atezolizumab in treating patients with localized muscle invasive bladder cancer. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as gemcitabine, cisplatin, fluorouracil and mitomycin-C, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab with radiation therapy and chemotherapy may work better in treating patients with localized muscle invasive bladder cancer compared to radiation therapy and chemotherapy without atezolizumab.
Patients must have histologically proven, T2-T4a N0M0 urothelial carcinoma of the bladder within 70 days prior to randomization. Patients with mixed urothelial carcinoma will be eligible for the trial, but the presence of small cell carcinoma will make a patient ineligible. Patients must undergo a transurethral resection of bladder tumor (TURBT) within 70 days prior to randomization. Patient must not have T4b disease.Patient must not have had prior pelvic radiation.Patients must not have received prior treatment for muscle invasive bladder cancer including neoadjuvant chemotherapy for the current tumor. Patients must not have received any systemic therapy (including, but not limited to, interferon alfa-2b, high dose IL-2, pegylated interferon [PEG-IFN], anti-PD-1, anti-PD-L1), for non-muscle invasive bladder cancer. Prior intravesical BCG, interferon, and intravesical chemotherapy are allowed.
Active Comparator: Arm I (RT, chemotherapy)Patients undergo RT (3D CRT or IMRT) Monday-Friday for up to 7 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine IV twice weekly for 6 weeks, or cisplatin IV weekly for 6 weeks concurrent with RT, or fluorouracil IV on same days as doses 1-5 and 16-20 of radiation therapy, and mitomycin IV on day 1 of radiation therapy in the absence of disease progression or unacceptable toxicity.Experimental: Arm II (RT, chemotherapy, atezolizumab)Patients undergo RT (3DCRT or IMRT) Monday-Friday for up to 7 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 60 minutes on day 1 of chemotherapy. Treatment repeats every 21 days for a total of 6 months (9 doses total) in the absence of disease progression or unacceptable toxicity.
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