search
Back to results

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

Primary Purpose

Bladder Cancer

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Atezolizumab
Sponsored by
UNICANCER
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Institut BergonieRecruiting
  • Centre Jean PerrinRecruiting
  • Centre Georges Francois LeclercRecruiting
  • Centre Oscar LambretRecruiting
  • Icm Val D'AurelleRecruiting
  • Centre Azureen de CancerologieRecruiting
  • Centre Antoine LacassagneRecruiting
  • Hopital Saint LouisRecruiting
  • Hôpital Pitie SalpetriereRecruiting
  • Chu Lyon SudRecruiting
  • Centre Eugene Marquis
  • INSTITUT de CANCEROLOGIE DE L'OUEST - site René GauducheauRecruiting
  • Institut de Cancerologie de LorraineRecruiting
  • Gustave Roussy

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

atezolizumab

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
October 2, 2018
Last Updated
July 5, 2022
Sponsor
UNICANCER
Collaborators
Roche Pharma AG
search

1. Study Identification

Unique Protocol Identification Number
NCT03697850
Brief Title
Atezolizumab After Chemo-radiotherapy for MIBC Patients Not Eligible for Radical Cystectomy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 14, 2018 (Actual)
Primary Completion Date
June 15, 2025 (Anticipated)
Study Completion Date
February 15, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
Collaborators
Roche Pharma AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
77 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
atezolizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Intervention Description
Atezolizumab after adjuvant radio-chemotherapy for the treatment of patients with muscle-invasive bladder cancer not eligible for radical cystectomy
Primary Outcome Measure Information:
Title
Disease Free Survival
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Local control rate
Description
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.
Time Frame
2 years
Title
Local control rate
Description
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.
Time Frame
5 years
Title
Disease Free Survival
Description
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.
Time Frame
5 years
Title
Overall Survival
Description
Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.
Time Frame
2 years
Title
Overall Survival
Description
Overall Survival is defined as the delay between the date of inclusion and the date of death, from any cause.
Time Frame
5 years
Title
Incidence of Treatment-Emergent Adverse Events
Description
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
Time Frame
2 years
Title
Incidence of Treatment-Emergent Adverse Events
Description
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
Time Frame
5 years
Title
Quality of Life Core Questionnaire - Cancer Patients (QLQ-C30)
Description
Quality of life
Time Frame
5 years
Title
Quality of Life Core Questionnaire - Bladder Cancer Muscle Invasive (QLQ-BLM30)
Description
Quality of Life
Time Frame
5 years
Title
Quality of Life Core Questionnaire - Elderly Cancer Patients (QLQ-ELD14)
Description
Quality of Life
Time Frame
5 years
Title
G8 oncodage
Description
Quality of Life
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Selection phase Inclusion Criteria: 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. Complete transurethral resection of bladder tumour (TURBT), either: within 6 weeks of selection if no chemotherapy was administered, or before starting chemotherapy. Patients for which chemo-radiotherapy is planned No major pelvic involvement: pelvic nodes ≤15 mm on CT scan. No distant metastasis. Patient unfit for radical cystectomy because of age, comorbidities, or patient's refusal. Patients ≥18 years old Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Life expectancy ≥12 months. 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. 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. Patients having provided written informed consent prior to any study-related procedures. Patients affiliated to the social security scheme. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol. 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: Prior pelvic irradiation. MIBC histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types). 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. 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. Contraindications for pelvic radiotherapy (e.g., inflammatory bowel disease). History of immunodeficiency, including HIV infection, or systemic steroid therapy for any other disease. A history of active autoimmune disease, except autoimmune-related hypothyroidism and type I diabetes mellitus (see appendix 5). History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins. Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation. Prior allogeneic stem cell or solid organ transplant. 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. Patients with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible. 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. Patients enrolled in another therapeutic study within 30 days of selection. Pregnant or breast feeding women. Person deprived of their liberty or under protective custody or guardianship. Inclusion phase Inclusion Criteria: Patients who have received standard (chemo)-radiotherapy ≥60 gray (Gy) or equivalent on the bladder according to the local practice. The first administration of atezolizumab must be performed 30 (+/-5) days after the last session of radiotherapy (RT). ECOG performance status ≤2. 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. 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. Patients having provided written informed consent prior to any study-related procedures. Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sandra PELISSIER
Phone
+33 1 44 23 55 68
Email
s-pelissier@unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christophe HENNEQUIN, Prof
Organizational Affiliation
Hôpital Saint Louis
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Bergonie
City
Bordeaux
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paul SARGOS, MD
Phone
+33 5 56 33 33 43
Email
p.sargos@bordeaux.unicancer.fr
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Geneviève LOOS, MD
Phone
+33 4 73 27 81 42
Email
genevieve.loos@clermont.unicancer.fr
Facility Name
Centre Georges Francois Leclerc
City
Dijon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Etienne MARTIN, MD
Phone
+33 3 80 73 75 28
Email
emartin@cgfl.fr
Facility Name
Centre Oscar Lambret
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David PASQUIER, MD
Email
d-pasquier@o-lambret.fr
Facility Name
Icm Val D'Aurelle
City
Montpellier
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David AZRIA, PhD
Phone
+33 4 67 61 31 32
Email
david.azria@montpellier.unicancer.fr
Facility Name
Centre Azureen de Cancerologie
City
Mougins
ZIP/Postal Code
06250
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe RONCHIN, MD
Phone
+33 4 94 52 11 82
Email
ronchinp@yahoo.fr
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Eve CHAND FOUCHE, MD
Phone
+33 4 92 03 12 61
Email
marie-eve.chand@nice.unicancer.fr
Facility Name
Hopital Saint Louis
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe HENNEQUIN, PhD
Phone
+33 1 42 49 90 24
Email
christophe.hennequin2@aphp.fr
Facility Name
Hôpital Pitie Salpetriere
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Morgan ROUPRÊT, PhD
Phone
+33 1 42 17 71 29
Email
mroupret@gmail.com
Facility Name
Chu Lyon Sud
City
Pierre-Bénite
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier CHAPET, PhD
Phone
+33 4 78 86 42 51
Email
Olivier.chapet@chu-lyon.fr
Facility Name
Centre Eugene Marquis
City
Rennes
Country
France
Individual Site Status
Withdrawn
Facility Name
INSTITUT de CANCEROLOGIE DE L'OUEST - site René Gauducheau
City
Saint-Herblain
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valentine GUIMAS, MD
Phone
+33 2 40 57 99 55
Email
Valentine.Guimas@ico.unicancer.fr
Facility Name
Institut de Cancerologie de Lorraine
City
Vandœuvre-lès-Nancy
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lionel GEOFFROIS, MD
Phone
+33 3 83 59 83 32
Email
l.geoffrois@nancy.unicancer.fr
Facility Name
Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre BLANCHARD, MD
Phone
+331 42 11 44 13
Email
pierre.blanchard@gustaveroussy.fr

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.

Learn more about this trial

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

We'll reach out to this number within 24 hrs