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

Bladder Cancer Clinical Trial

— BladderSpar  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03697850
• Other study ID #: UC-0160/1715
• Secondary ID: 2018-001807-35
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 14, 2018
• Est. completion date: February 15, 2029

Study information

• Verified date: November 2023
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 79
• Est. completion date: February 15, 2029
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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 Adequate renal function: clearance >50 mL/min (Cockcroft). Adequate hepatic function: Aspartate aminotransferase (AST [SGOT]) and Alanine aminotransferase (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 =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.

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.

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

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

Locations

Country	Name	City	State
France	Institut Bergonie	Bordeaux
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Georges Francois Leclerc	Dijon
France	Centre Oscar Lambret	Lille
France	Icm Val D'Aurelle	Montpellier
France	Centre Azureen de Cancerologie	Mougins
France	Centre Antoine Lacassagne	Nice
France	Hôpital Pitie Salpetriere	Paris
France	Hopital Saint Louis	Paris
France	Chu Lyon Sud	Pierre-Bénite
France	INSTITUT de CANCEROLOGIE DE L'OUEST - site René Gauducheau	Saint-Herblain
France	Institut de Cancerologie de Lorraine	Vandœuvre-lès-Nancy
France	Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
UNICANCER	Roche Pharma AG

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival	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.	2 years
Secondary	Local control rate	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.	2 years
Secondary	Local control rate	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.	5 years
Secondary	Disease Free Survival	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.	5 years
Secondary	Overall Survival	Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.	2 years
Secondary	Overall Survival	Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.	5 years
Secondary	Incidence of Treatment-Emergent Adverse Events	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	2 years
Secondary	Incidence of Treatment-Emergent Adverse Events	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	5 years
Secondary	Quality of Life Core Questionnaire - Cancer Patients (QLQ-C30)	Quality of life	5 years
Secondary	Quality of Life Core Questionnaire - Bladder Cancer Muscle Invasive (QLQ-BLM30)	Quality of Life	5 years
Secondary	Quality of Life Core Questionnaire - Elderly Cancer Patients (QLQ-ELD14)	Quality of Life	5 years
Secondary	G8 oncodage	Quality of Life	5 years