Atezolizumab After Chemo-radiotherapy for MIBC Patients Not Eligible for Radical Cystectomy

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Collaborators:

Information provided by (Responsible Party):

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Tracking Information

First Submitted Date ^ICMJE

October 2, 2018

First Posted Date ^ICMJE

October 5, 2018

Last Update Posted Date

October 5, 2018

Actual Study Start Date ^ICMJE

November 15, 2018

Estimated Primary Completion Date

January 15, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Disease Free Survival[ Time Frame: 2 years ]

Disease Free Survival is defined as the delay between date of inclusion and tumour relapse (local, regional, or distant) or death from any cause, whichever occurs first.

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Local control rate[ Time Frame: 2 years ]
Local control rate will be evaluated by cystoscopy. The presence of non-muscle-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.
Local control rate[ Time Frame: 5 years ]
Local control rate will be evaluated by cystoscopy. The presence of non-muscle-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.
Disease Free Survival[ Time Frame: 5 years ]
Disease Free Survival is defined as the delay between date of inclusion and tumour relapse (local, regional, or distant) or death from any cause, whichever occurs first.
Overall Survival[ Time Frame: 2 years ]
Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.
Overall Survival[ Time Frame: 5 years ]
Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.
Incidence of Treatment-Emergent Adverse Events[ Time Frame: 2 years ]
The tolerance and safety will be evaluated by toxicity (acute [<6 months after the start of atezolizumab] and late [≥6 months after the start of atezolizumab]), assessed using the NCI CTCAE v5.0
Incidence of Treatment-Emergent Adverse Events[ Time Frame: 5 years ]
The tolerance and safety will be evaluated by toxicity (acute [<6 months after the start of atezolizumab] and late [≥6 months after the start of atezolizumab]), assessed using the NCI CTCAE v5.0
Quality of Life Core Questionnaire - Cancer Patients (QLQ-C30)[ Time Frame: 5 years ]
Quality of life
Quality of Life Core Questionnaire - Bladder Cancer Muscle Invasive (QLQ-BLM30)[ Time Frame: 5 years ]
Quality of Life
Quality of Life Core Questionnaire - Ederly Cancer Patients (QLQ-ELD14)[ Time Frame: 5 years ]
Quality of Life
G8 oncodage[ Time Frame: 5 years ]
Quality of Life

Descriptive Information

Brief Title ^ICMJE

Atezolizumab After Chemo-radiotherapy for MIBC Patients Not Eligible for Radical Cystectomy

Official Title ^ICMJE

Phase II Study of Maintenance Anti-PD-L1 Treatment With Atezolizumab After Chemo-radiotherapy for Muscle-infiltrating Bladder Cancer Patients Not Eligible for Radical Cystectomy: Bladder Sparing

Brief Summary

Patients older than ≥18 years, with muscle-invasive bladder cancer unfit for radical cystectomy because of age, comorbidities, and/or patient's refusal. This study is designed as a multicentre, single-arm phase II study.

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Allocation:
Intervention Model: Single Group Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: Atezolizumab
Atezolizumab after adjuvant radio-chemotherapy for the treatment of patients with muscle-invasive bladder cancer not eligible for radical cystectomy

Study Arms

Experimental: atezolizumab
Anti-PD-L1 immunotherapy: atezolizumab (1200 mg) administered IV over 1 h every 3 weeks for 12 months (18 injections). Beginning 30 days (±5 days) after chemo-radiotherapy.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

January 15, 2025

Estimated Primary Completion Date

January 15, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Selection phase Inclusion Criteria: 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. 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. Eastern Cooperative Oncology Group (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 upper limit of normal (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. Exclusion 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 Inclusion Criteria: 1. Patients who have received standard (chemo)-radiotherapy ≥60 gray (Gy) 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 radiotherapy (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 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. Exclusion Criteria: The same non-inclusion criteria of the selection phase have to be respected.

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

France

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

UNICANCER

Collaborators ^ICMJE

Investigators ^ICMJE

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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