A

Phase 1

• Conditions: Patients older than =18 years, muscle-invasive bladder cancer unfit for radical cystectomy because of age, comorbidities, and/or patient’s refusal.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001807-35-FR
• Lead Sponsor: ICANCER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-08-21
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 77

Inclusion Criteria

SELECTION PHASE
1 Muscle-invasive bladder cancer (MIBC) pT2-T3 histologically confirmed:
•Urothelial and squamous cell histological types are allowed.
•De novo MIBC or after a history of non-muscle-invasive bladder cancer.
•In case of extensive or multifocal bladder carcinoma in situ (CIS), cystectomy is the treatment of choice. However, if cystectomy is impossible, these patients are eligible if chemo-radiotherapy is planned.
2.Complete transurethral resection of bladder tumour (TURBT), either:
within 6 weeks of selection if no chemotherapy was administered,
or
before starting chemotherapy.
3.Patients for which chemo-radiotherapy is planned
4.No major pelvic involvement: pelvic nodes =15 mm on CT scan.
5.No distant metastasis.
6.Patient unfit for radical cystectomy because of age, comorbidities, or patient’s refusal.
7.Patients =18 years old
8.ECOG performance status =2.
9 Life expectancy =12 months.
10 Haematological and biological parameters:
•White blood cell count =4000/mm3
•Platelet count =100000 cells/mm3
•Haemoglobin level =9 g/dL or corrected after transfusion
•A glomerular filtration rate =25 mL/min.
•Adequate renal function: clearance >50 mL/min (MDRD).
•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.
11.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.
12.Patients having provided written informed consent prior to any study-related procedures.
13.Patients affiliated to the social security scheme.
14.Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
15.Patient consents to the use of their collected tumour specimen, as well as, blood samples as detailed in the protocol for future scientific research which includes but not limited to DNA, RNA, and protein-based biomarker detection.I

INCLUSION PHASE
1.Patients who have received standard (chemo)-radiotherapy =60Gy or equivalent on the bladder according to the local practice.
2.The first administration of atezolizumab must be performed 30 (+/-5) days after the last session of RT.
3.ECOG performance status =2.
4.Haematological and biological parameters:
•White blood cell count =4000/mm3
•Platelet count =100000 cells/mm3
•Haemoglobin level =9 g/dL or corrected after transfusion
•A glomerular filtration rate =25 mL/min
•Adequate renal function: clearance >50 mL/min (MDRD)
•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.
5.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.
6.Patients having provided written informed consent prior to any study-related procedures.
7.Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
8.Patient consents

Exclusion Criteria

SELECTION PHASE
Patients are not eligible if they comply with any of the following criteria:
1.Prior pelvic irradiation.
2.MIBC histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types).
3.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.
4.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.
5.Contraindications for pelvic radiotherapy (e.g., inflammatory bowel disease).
6.History of immunodeficiency, including HIV infection, or systemic steroid therapy for any other disease.
7.A history of active autoimmune disease, except autoimmune-related hypothyroidism and type I diabetes mellitus (see appendix 5).
8.History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.
9.Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation.
10.Prior allogeneic stem cell or solid organ transplant.
11.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.
12.Patients with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible.
13.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.
14.Patients enrolled in another therapeutic study within 30 days of selection.
15.Pregnant or breast feeding women.
16.Person deprived of their liberty or under protective custody or guardianship.

INCLUSION PHASE
The same non-inclusion criteria of selection phase have to be respected.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: •To evaluate local control at 2 and 5 years.<br>•To evaluate disease-free survival (DFS) at 5 years.<br>•To evaluate overall survival (OS) at 2 and 5 years.<br>•To evaluate the tolerance and safety of the treatment strategy.<br>•To evaluate patients’ quality of life<br>;Primary end point(s): Disease-free survival (DFS) will be assessed at 2 years. DFS is defined as the delay between date of inclusion and tumour relapse (local, regional, or distant) or death from any cause, whichever occurs first.<br>;Timepoint(s) of evaluation of this end point: 2 years;Main Objective: The primary objective of this study is to evaluate the efficacy of a maintenance therapy with atezolizumab, an anti-PD-L1, after adjuvant chemo-radiotherapy for the treatment of patients with muscle-invasive bladder cancer not eligible for radical cystectomy, in terms of disease-free survival (DFS) assessed at 2 years.