ATEZOLIZUMAB for Non-muscle invasive bladder cancer (high-risk)

Inclusion criteria

• {"criterion_text":"- Signed informed consent form after the last endoscopic surgery"}
• {"criterion_text":"- Absence of metastasis in the pelvis, abdomen, or chest, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan no more than 90 days prior to the first study treatment"}
• {"criterion_text":"- ECOG performance status of ≤ 2"}
• {"criterion_text":"- Life expectancy ≥ 12 weeks"}
• {"criterion_text":"- Systolic blood pressure (BP) <160 mmHg and diastolic BP <95 mmHg, as documented within 7 days prior to the first study treatment (hypertension allowed provided it is controlled)"}
• {"criterion_text":"- Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 7 days prior to the first study treatment"}
• {"criterion_text":"- Patients affiliated to the social security system"}
• {"criterion_text":"- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab"}
• {"criterion_text":"- Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up"}
• {"criterion_text":"- Adult men and women ( age ≥ 18 years)"}
• {"criterion_text":"- Any high risk non muscle invasive urothelial carcinoma histologically confirmed (mixed histology tumors allowed if urothelial carcinoma histology is predominant) defined on the TURBT"}
• {"criterion_text":"- Tumor tissue available from the surgery for central confirmation of the diagnosis and analysis the expression of PD-L1. In case of a second TURBT performed, as per Belgian guidelines, the tumour tissue from the TURBT procedure that supports the primary diagnosis for study eligibility should be the tumour tissue used for the PD-L1 expression testing (applicable only in Belgium)"}
• {"criterion_text":"- At least one additional (second) resection of the primary tumor has been performed"}

Exclusion criteria

• {"criterion_text":"- Patient having received previous BCG therapy for bladder cancer. In addition, for Belgium, patients who have received prior radiation therapy will not be eligible."}
• {"criterion_text":"- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation if such a live, attenuated vaccine will be required during the study"}
• {"criterion_text":"- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications"}
• {"criterion_text":"- Any approved anti-cancer therapy, including systemic chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment. Hormone-replacement therapy or oral contraceptives are allowed"}
• {"criterion_text":"- Prior treatment with CD137 agonists or immune checkpoint−blockade therapies, including anti-CD40, anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies"}
• {"criterion_text":"- Treatment with systemic immunostimulatory agents (including but not limited to interferons, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1"}
• {"criterion_text":"- Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial"}
• {"criterion_text":"- Serum albumin < 2.5 g/dL"}
• {"criterion_text":"- For France and Belgium, person deprived of their liberty or under protective custody or guardianship"}
• {"criterion_text":"- For France, patients who have previously experienced a pericardial disorder on prior treatment with other immune-stimulatory anticancer agents."}
• {"criterion_text":"- For Belgium: Any contra-indications for the adjuvant intravesical BCG treatment"}
• {"criterion_text":"- Known HIV infection"}
• {"criterion_text":"- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to day 1 of study treatment"}
• {"criterion_text":"- Malignancies other than UC within 5 years prior to Day 1 of cycle 1 of treatment apart certain exceptions"}
• {"criterion_text":"- Pregnancy or breastfeeding"}
• {"criterion_text":"- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins"}
• {"criterion_text":"- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation"}
• {"criterion_text":"- History of autoimmune disease or history of immunosuppression, or conditions associated with congenital or acquired immune deficiency , including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis."}
• {"criterion_text":"- Patients with active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test prior to randomization) or hepatitis C."}
• {"criterion_text":"- Known active tuberculosis"}
• {"criterion_text":"- Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia."}
• {"criterion_text":"- Signs or symptoms of urinary infection and/or other signs and symptoms > grade 1 (NCI CTCAE v5.0) within 2 weeks prior to Cycle 1, Day 1. Patients receiving therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 are not eligible. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible."}
• {"criterion_text":"- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months before Cycle 1, Day 1, unstable arrhythmias, or unstable angina."}
• {"criterion_text":"- Major surgical procedure other than for diagnosis within 4 weeks prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study"}
• {"criterion_text":"- Prior allogeneic stem cell or solid organ transplant"}

Primary endpoints

• {"endpoint_text":"- Event-free survival defined as the time from randomization to the time of first EFS event.","definition_or_measurement_approach":"Defined as the time from randomization to the time of first event-free survival (EFS) event (time-to-event)."}

Secondary endpoints

• {"endpoint_text":"- High-grade recurrence-free survival is defined by reappearance of high risk disease (high grade, T1 or CIS)","definition_or_measurement_approach":"Defined by reappearance of high-risk disease (high grade, T1 or CIS); time-to-event measure."}
• {"endpoint_text":"- Progression-free survival is defined as the time from randomization to the date of progression or death. Progression is defined as increase of stage from Ta to T1 or from CIS to T1; progression to MIBC (T≥ 2) or to lymph node N+ or to distant disease M+","definition_or_measurement_approach":"Time from randomization to progression or death; progression criteria specified (stage increases to T1, MIBC T≥2, N+ or M+)."}
• {"endpoint_text":"- Disease-specific survival defined as the time from randomization to the date of death from bladder cancer;","definition_or_measurement_approach":"Time from randomization to death due to bladder cancer."}
• {"endpoint_text":"- Overall Survival, defined as the time from randomization to the date of death from any cause","definition_or_measurement_approach":"Time from randomization to death from any cause."}
• {"endpoint_text":"- Disease worsening, defined as cystectomy or indicative change in therapy, including systemic chemotherapy or radiation therapy. The date of diagnosis (cystoscopy or CT) leading to cystectomy or chemotherapy/radiotherapy will be considered as the time of disease worsening","definition_or_measurement_approach":"Defined as occurrence of cystectomy or change to systemic chemotherapy/radiation therapy; date of diagnosis leading to intervention used as event date."}
• {"endpoint_text":"- Complete response will be measured among patients with CIS disease with or without papillary tumor at diagnosis, Week 12, Week 51, and 2 years after randomization. It will be defined by normal cystoscopy and normal cytology.","definition_or_measurement_approach":"Assessed at Week 12, Week 51 and 2 years post-randomization; defined as normal cystoscopy and normal cytology."}
• {"endpoint_text":"- Duration of response (DOR) is defined as the interval from response initiation (when either complete or partial response is first determined) to progression or death, whichever occurs first.","definition_or_measurement_approach":"Interval from first documented response (complete or partial) to progression or death."}
• {"endpoint_text":"- Frequency, nature, and severity of adverse events graded according to NCI CTCAE v5.0 and immune-related event (irAE)","definition_or_measurement_approach":"AE collection and grading per NCI CTCAE v5.0; immune-related AEs recorded and characterized."}
• {"endpoint_text":"- Quality of life will be measured using EORTC QLQ-C30 assessed at baseline and then every 12 weeks for year 1-2 then every 24 weeks for year 3-5","definition_or_measurement_approach":"Quality of life measured by EORTC QLQ-C30 at baseline, every 12 weeks during years 1-2, then every 24 weeks during years 3-5."}
• {"endpoint_text":"- Status of tumor immune-related biomarkers in archival and /or freshly obtained tissues;","definition_or_measurement_approach":"Assessment of tumor immune-related biomarkers in archival and/or fresh tissues; methods not specified in dataset."}
• {"endpoint_text":"- Status of exploratory biomarkers in urine, plasma, whole blood collected before and during treatment with atezolizumab or at recurrence and association with outcome","definition_or_measurement_approach":"Exploratory biomarker analysis in urine, plasma, whole blood collected pre- and on-treatment and at recurrence, correlated with outcomes."}

Belgium

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

04-11-2024

Processing Time Days

62

Number Of Sites

2

Number Of Participants

17

France

Earliest CTIS Part Ii Submission Date

06-12-2024

Latest Decision Or Authorization Date

31-12-2024

Processing Time Days

25

Number Of Sites

54

Number Of Participants

463

Spain

Earliest CTIS Part Ii Submission Date

03-09-2024

Latest Decision Or Authorization Date

30-10-2024

Processing Time Days

57

Number Of Sites

9

Number Of Participants

37

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"F. Hoffmann-La Roche Ltd","duties_or_roles":"Monetary support","organisation_type":""}