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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Anticipated): 77
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sandra PELISSIER; Phone Number: +33 1 44 23 55 68; Email: s-pelissier@unicancer.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • Institut Bergonié
    • Contact: Paul SARGOS, MD; Phone Number: +33 5 56 33 33 43; Email: p.sargos@bordeaux.unicancer.fr
  • Clermont-Ferrand, France
    • Recruiting
    • Centre Jean Perrin
    • Contact: Geneviève LOOS, MD; Phone Number: +33 4 73 27 81 42; Email: genevieve.loos@clermont.unicancer.fr
  • Dijon, France
    • Recruiting
    • Centre Georges François Leclerc
    • Contact: Etienne MARTIN, MD; Phone Number: +33 3 80 73 75 28; Email: emartin@cgfl.fr
  • Lille, France
    • Recruiting
    • Centre Oscar Lambret
    • Contact: David PASQUIER, MD; Email: d-pasquier@o-lambret.fr
  • Montpellier, France
    • Recruiting
    • ICM Val d'Aurelle
    • Contact: David AZRIA, PhD; Phone Number: +33 4 67 61 31 32; Email: david.azria@montpellier.unicancer.fr
  • Mougins, France, 06250
    • Recruiting
    • Centre Azuréen de Cancérologie
    • Contact: Philippe RONCHIN, MD; Phone Number: +33 4 94 52 11 82; Email: ronchinp@yahoo.fr
  • Nice, France
    • Recruiting
    • Centre Antoine Lacassagne
    • Contact: Marie Eve CHAND FOUCHE, MD; Phone Number: +33 4 92 03 12 61; Email: marie-eve.chand@nice.unicancer.fr
  • Paris, France
    • Recruiting
    • Hôpital Saint Louis
    • Contact: Christophe HENNEQUIN, PhD; Phone Number: +33 1 42 49 90 24; Email: christophe.hennequin2@aphp.fr
  • Paris, France
    • Recruiting
    • Hopital Pitie Salpetriere
    • Contact: Morgan ROUPRÊT, PhD; Phone Number: +33 1 42 17 71 29; Email: mroupret@gmail.com
  • Pierre-Bénite, France
    • Recruiting
    • CHU Lyon Sud
    • Contact: Olivier CHAPET, PhD; Phone Number: +33 4 78 86 42 51; Email: Olivier.chapet@chu-lyon.fr
  • Rennes, France
    • Withdrawn
    • Centre Eugène Marquis
  • Saint-Herblain, France
    • Recruiting
    • Institut de Cancérologie de l'Ouest - Site René Gauducheau
    • Contact: Valentine GUIMAS, MD; Phone Number: +33 2 40 57 99 55; Email: Valentine.Guimas@ico.unicancer.fr
  • Vandœuvre-lès-Nancy, France
    • Recruiting
    • Institut de cancérologie de Lorraine
    • Contact: Lionel GEOFFROIS, MD; Phone Number: +33 3 83 59 83 32; Email: l.geoffrois@nancy.unicancer.fr
  • Villejuif, France, 94800
    • Not yet recruiting
    • Gustave Roussy
    • Contact: Pierre BLANCHARD, MD; Phone Number: +331 42 11 44 13; Email: pierre.blanchard@gustaveroussy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Atezolizumab; Atezolizumab after adjuvant radio-chemotherapy for the treatment of patients with muscle-invasive bladder cancer not eligible for radical cystectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Overall Survival	Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.	2 years
Overall Survival	Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.	5 years
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
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
Quality of Life Core Questionnaire - Cancer Patients (QLQ-C30)	Quality of life	5 years
Quality of Life Core Questionnaire - Bladder Cancer Muscle Invasive (QLQ-BLM30)	Quality of Life	5 years
Quality of Life Core Questionnaire - Elderly Cancer Patients (QLQ-ELD14)	Quality of Life	5 years
G8 oncodage	Quality of Life	5 years

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Christophe HENNEQUIN, Prof, Hôpital Saint Louis

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Anticipated): June 15, 2025
• Study Completion (Anticipated): February 15, 2029

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Antineoplastic Agents; Atezolizumab
• Other Study ID Numbers: UC-0160/1715; 2018-001807-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No