ATEZOLIZUMAB for Muscle-invasive bladder cancer

Inclusion criteria

• {"criterion_text":"- Selection phase : Muscle-invasive bladder cancer (MIBC) pT2-T3 histologically confirmed\n- Selection phase : Haematological and biological parameters : White blood cell count ≥4000/mm3; Platelet count ≥100000 cells/mm3; Haemoglobin level ≥9 g/dL or corrected after transfusion; Adequate renal function: clearance >50 mL/min (Cockcroft); Adequate hepatic function: AST (SGOT) and ALT (SGPT) ≤2.5 x ULN, or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible.\n- Selection phase : Patients of childbearing potential who agree to use a medically acceptable method of contraception during the study and for 120 days after the last study treatment. Women must have a negative urine or serum pregnancy test before receiving the study treatment and within 14 days prior to selection.\n- Selection phase : Patients having provided written informed consent prior to any study-related procedures.\n- Selection phase : Patients affiliated to the social security scheme.\n- Selection phase : Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.\n- Inclusion phase : Patients who have received standard (chemo)-radiotherapy ≥60Gy or equivalent on the bladder according to the local practice.\n- Inclusion phase : The first administration of atezolizumab must be performed within 30 (+/-5) days after the last session of RT.\n- Inclusion phase : ECOG performance status ≤2.\n- Inclusion phase : Haematological and biological parameters : White blood cell count ≥3000/mm3; Platelet count ≥100000 cells/mm3; Haemoglobin level ≥9 g/dL or corrected after transfusion; Adequate renal function: clearance >50 mL/min (Cockcroft); Adequate hepatic function: AST (SGOT) and ALT (SGPT) ≤2.5 x ULN, or ≤3.5 x ULN in the case of concurrent disease with known etiology and for which a corrective treatment is possible; Adequate cardiac function: Troponin and CPK-MB at normal range.\n- Inclusion phase : Patients of childbearing potential who agree to use a medically acceptable method of contraception during the study and for 120 days after the last study treatment. Women must have a negative urine or serum pregnancy test before receiving the study treatment and within 14 days prior to inclusion.\n- Selection phase : Complete transurethral resection of bladder tumour (TURBT)\n- Inclusion phase : Patients having provided written informed consent prior to any study-related procedures.\n- Inclusion phase : Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.\n- Selection phase : Patients for which chemo-radiotherapy is planned\n- Selection phase : No major pelvic involvement: pelvic nodes ≤15 mm on CT scan\n- Selection phase : No distant metastasis\n- Selection phase : Patient unfit for radical cystectomy because of age, comorbidities, or patient’s refusal\n- Selection phase : Patients ≥18 years old\n- Selection phase : ECOG performance status ≤2\n- Selection phase : Life expectancy ≥12 months"}

Exclusion criteria

• {"criterion_text":"- Selection phase : Patient with bladder carcinoma in situ (CIS).\n- Inclusion phase : In addition to the same non-inclusion criteria of selection phase that have to be respected, patients who have previously experienced a severe cutaneous reaction during previous treatment with an immune-stimulating anti-cancer agent.\n- Selection phase : Prior pelvic irradiation.\n- Selection phase : MIBC histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types).\n- Selection phase : History of neoplastic disease, during the 3 years before selection, except completely resected cutaneous basal-cell carcinomas, carcinoma in-situ or localised prostate cancer without biochemical recurrence following definitive treatment.\n- Selection phase : Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death-1 receptor (anti- PD-1), and anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibodies.\n- Selection phase : Contraindications for pelvic radiotherapy (e.g., inflammatory bowel disease).\n- Selection phase : History of immunodeficiency, including HIV infection, or systemic steroid therapy for any other disease.\n- Selection phase : A history of active autoimmune disease, except autoimmune-related hypothyroidism and type I diabetes mellitus\n- Selection phase : History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.\n- Selection phase : Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation.\n- Selection phase : Prior allogeneic stem cell or solid organ transplant.\n- Selection phase : Patients with the following severe acute co-morbidity are not eligible : Unstable angina or congestive heart failure that required hospitalisation in the 6 months before selection; Transmural myocardial infarction in the 6 months prior to selection; Acute bacterial or fungal infection requiring intravenous antibiotics at selection; Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalisation or precluding study therapy at the time of selection; Severe hepatic disease: Child-Pugh Class B or C.\n- Selection phase : Patients with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible.\n- Selection phase : Patients unable to comply with study obligations for geographic, social, or physical reasons, or who are unable to understand the purpose and procedures of the study.\n- Selection phase : Patients enrolled in another therapeutic study within 30 days of selection.\n- Selection phase : Pregnant or breast feeding women.\n- Selection phase : Person deprived of their liberty or under protective custody or guardianship."}

Primary endpoints

• {"endpoint_text":"- Disease-free survival (DFS) will be assessed at 2 years. DFS is defined as the delay between date of inclusion, and tumour progression (local, regional, or distant) or death of any cause, whichever occurs first.","definition_or_measurement_approach":"DFS is defined as the delay between date of inclusion, and tumour progression (local, regional, or distant) or death of any cause, whichever occurs first; assessed at 2 years."}

Secondary endpoints

• {"endpoint_text":"- Local control rate will be evaluated by cystoscopy at 2 and 5 years. The presence of nonmuscle- invasive or muscle-invasive bladder cancers will be considered as a local failure. To be defined as locally controlled, the bladder must be completely free of tumour. Duration of local control will be calculated from the date of inclusion till the date of positive cystoscopy. In case of regional or distant relapse occurring before local relapse, data will be censored at the time of relapse.","definition_or_measurement_approach":"Local control rate measured by cystoscopy at 2 and 5 years; local failure defined by presence of nonmuscle-invasive or muscle-invasive bladder cancers; duration from inclusion to positive cystoscopy; censoring if regional/distant relapse occurs first."}
• {"endpoint_text":"- Disease-free survival (DFS) will be assessed at 5 years. DFS is defined as the delay between date of inclusion, and tumour progression (local, regional, or distant) or death of any cause, whichever occurs first.","definition_or_measurement_approach":"DFS as defined above, assessed at 5 years."}
• {"endpoint_text":"- Overall Survival (OS) will be assessed at 2 and 5 years. OS is defined as the delay between the date of inclusion and the date of death, of any cause.","definition_or_measurement_approach":"OS defined as time from inclusion to death from any cause; assessed at 2 and 5 years."}
• {"endpoint_text":"- The tolerance and safety will be evaluated by toxicity: acute (<6 months after the start of treatment) and late (≥6 months after the start of treatment), assessed using the NCI CTCAE v5.0 (see Appendix 2). The tolerance will be evaluated up until 5 years.","definition_or_measurement_approach":"Toxicity graded by NCI CTCAE v5.0; acute <6 months and late ≥6 months after start of treatment; tolerance evaluated up to 5 years."}
• {"endpoint_text":"- Quality of life","definition_or_measurement_approach":"Quality of life (measurement instrument not specified in provided data)."}

France

Earliest CTIS Part Ii Submission Date

24-04-2024

Latest Decision Or Authorization Date

24-05-2024

Processing Time Days

30

Number Of Sites

14

Number Of Participants

77

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Roche","duties_or_roles":"Source of monetary support","organisation_type":""}