Last updated on August 2020

Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer


Brief description of study

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.

Detailed Study Description

PRIMARY OBJECTIVES:

I. To compare bladder intact event-free survival (BI-EFS) for concurrent chemoradiation therapy (CRT) with and without atezolizumab in localized muscle invasive bladder cancer (MIBC).

SECONDARY OBJECTIVES:

I. To compare overall survival between the two arms. II. To compare modified bladder intact event-free survival including cancer related death between arms.

III. To compare complete and partial pathologic response between arms at 3 months after completing chemoradiation therapy.

IV. To estimate metastases-free survival by arm. V. To compare the qualitative and quantitative adverse events from each arm. VI. To estimate the rate of non-muscle invasive bladder cancer recurrence by arm.

VII. To estimate the rate of salvage cystectomy and reasons for cystectomy by arm.

VIII. To compare mean patient-reported global quality of life (QOL) at week 54 using the European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ)-Core (C)30 Global Health Status (GHS) subscale score between patients with localized muscle-invasive bladder cancer randomized to chemoradiation with versus (vs.) without atezolizumab.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To test the hypothesis that a panel of validated biomarkers of concurrent CRT involving nuclear MRE11, impaired deoxyribonucleic acid damage response (DDR) function and tumor subtyping will be prognostic for BI-EFS among patients receiving either concurrent CRT or chemoimmuno-radiotherapy (CIRT) of the primary tumor.

II. To test the hypothesis that tumor total mutation burden, neoantigen burden, infiltrating immune response, PD-L1 expression and T cell response are associated with augmented response after concurrent CIRT.

III. To bank urine specimens for future use.

PATIENT-REPORTED OUTCOMES (PROs) OBJECTIVES:

I. To compare mean patient-reported global QOL as measured by the EORTC QLQ-C30 Global Health Status subscale scores at week 54 between patients with localized muscle-invasive bladder cancer randomized to chemoradiation with versus without atezolizumab.

II. To compare mean patient-reported bowel symptoms at each assessment time by arm using the Bowel Domain of the Expanded Prostate Index (EPIC- 26) short form, the bladder-specific supplement to the QLQ-C30, the EORTC QLQ-Muscle Invasive Bladder Cancer (BLM30), the Physical Functioning subscale of the EORTC QLQ-C30, and overall health status using the EuroQol Five Dimension Five Level Scale (EQ-5D-5L).

III. To compare longitudinal change over time by arm in patient-reported global QOL using the EORTC QLQ-C30, the Bowel Domain of the Expanded Prostate Index (EPIC-26) short form, the bladder-specific supplement to the QLQ-C30, the EORTC QLQ-BLM30, the Physical Functioning subscale of the EORTC QLQ-C30, and overall health status using the EQ-5D-5L.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo radiation therapy (RT) (3 dimensional [D] CRT or intensity-modulated radiation therapy [IMRT]) Monday-Friday for up to 7 weeks. Patients also receive chemotherapy based on physician's choice of gemcitabine intravenously (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.

ARM II: 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.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 1 year, and then annually for 3 years.

Clinical Study Identifier: NCT03775265

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Weisberg Cancer Treatment Center

Farmington Hills, MI United States
8.14miles
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Recruitment Status: Open


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