The purpose of this study is to assess the efficacy and safety of adding the immunotherapy Avelumab as a fourth component, alongside tumor removal, chemotherapy, and radiation, to increase the chance of preserving the bladder in the treatment of muscle-invasive bladder cancer.
Muscle-invasive bladder cancer (MIBC) is an aggressive form of bladder cancer, with a 5-year survival rate of about 40%. The standard treatment for MIBC is induction platinum-based chemotherapy followed by radical cystectomy. Recently bladder preservation strategies have emerged as an alternative to radical cystectomy, particularly useful for patients who are unfit for surgery or would rather opt for non-surgical approaches. Knowing the high risks related to surgery and its significant complications, the investigators propose to implement 2 tetra-modalities treatment strategies to increase the chance of preserving the bladder and decrease the need of salvage cystectomy. The purpose of this study is to assess the efficacy and safety of 2 bladder-preservation treatments plans called tetra-modalities: First plan: * maximium TURBT * chemo-immunotherapy as induction phase (Avelumab added to chemotherapy) * radiation therapy * maintenance phase with Avelumab Second plan: * Maximum TURBT * chemo-immunotherapy as induction phase (Avelumab added to chemotherapy) * radiation therapy * Watch and wait Both tetra-modalities duration will last maximum of 2 years from patient inclusion. These treatment plans are based on the synergistic action between immunotherapy, chemotherapy, and radiotherapy. The use of Avelumab in the maintenance group is supported by its proven success in treating advanced cancer and various studies looking at immunotherapy as a way to avoid or delay bladder removal.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Total removal of the bladder tumor through TURBT
Chemotherapy: DDMVAC (6 cycles) or Gemcitabine-Cisplatin (4 cycles) Immunotherapy: Avelumab (6 cycles)
Hypofractionated radiotherapy: 20 fractions, 55 Grays
American University of Beirut
Beirut, Beyrouth, Lebanon
Efficacy of Avelumab in 2 non-comparative arms
2 years proportion of MIBC bladder preserved participants in each tetra-modality arm.
Time frame: 2 years
Response rate post-induction
Response rate of participants in each arm following induction chemo/immunotherapy
Time frame: At week 17 (after 4 months of induction)
Quality of life
Effect of each tetra-modality arm on the quality of life of participants using the Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) questionnaire; FACT-Bl total score range: 0-156 (higher scores mean worse quality of life)
Time frame: Every 3 weeks (up to 3 months), then every 4 months (up to 1 year)
Safety
Incidence of Treatment-Emergent Adverse Events \[Safety and Tolerability\]
Time frame: During treatment (up to 90 days after end of treatment)
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Maintenance Avelumab every 2 weeks for 12 months
1 year watch and wait