Clinical trial NCT03697850: Atezolizumab After Chemo-radiotherapy for MIBC Patients Not Eligible for Radical Cystectomy
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Bladder Cancer
Lead sponsor: UNICANCER
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2018-10-05
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Disease Free Survival
timeFrame: 2 years
Secondary outcomes:
measure: Local control rate
timeFrame: 2 years
measure: Local control rate
timeFrame: 5 years
measure: Disease Free Survival
timeFrame: 5 years
measure: Overall Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 5 years
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 2 years
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 5 years
measure: Quality of Life Core Questionnaire - Cancer Patients (QLQ-C30)
timeFrame: 5 years
measure: Quality of Life Core Questionnaire - Bladder Cancer Muscle Invasive (QLQ-BLM30)
timeFrame: 5 years
measure: Quality of Life Core Questionnaire - Elderly Cancer Patients (QLQ-ELD14)
timeFrame: 5 years
measure: G8 oncodage
timeFrame: 5 years
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Montpellier
country: France
facility: Icm Val D'Aurelle
city: Mougins
country: France
facility: Centre Azureen de Cancerologie
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hôpital Pitie Salpetriere
city: Pierre-Bénite
country: France
facility: Chu Lyon Sud
city: Saint-Herblain
country: France
facility: INSTITUT de CANCEROLOGIE DE L'OUEST - site René Gauducheau
city: Villejuif
country: France
facility: Gustave Roussy
Study officials:
affiliation: Hôpital Saint Louis
name: Christophe HENNEQUIN, Prof
role: PRINCIPAL_INVESTIGATOR
References: