Atezolizumab After Chemo-radiotherapy for muscle-invasive bladder cancer Patients Not Eligible for Radical Cystectomy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

19 Feb 2019 → ongoing

Decision date (initial)

2024-05-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Roche

External identifiers

EU CT number

2024-512002-26-00

EudraCT number

2018-001807-35

ClinicalTrials.gov

NCT03697850

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of this study is to evaluate the efficacy of maintenance therapy with atezolizumab, an anti-PD-L1, after chemo-radiotherapy for the treatment of patients with muscleinvasive bladder cancer not eligible for radical cystectomy, in terms of the disease-free survival (DFS) assessed at 2 years.

Secondary objectives 5

1. To evaluate local control at 2 and 5 years.
2. To evaluate DFS at 5 years.
3. To evaluate overall survival (OS) at 2 and 5 years.
4. To evaluate the tolerance and safety of the treatment strategy.
5. To evaluate patients’ quality of life.

Conditions and MedDRA coding

Muscle-invasive bladder cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 21

1. Selection phase : Muscle-invasive bladder cancer (MIBC) pT2-T3 histologically confirmed
2. Selection phase : Complete transurethral resection of bladder tumour (TURBT)
3. Selection phase : Patients for which chemo-radiotherapy is planned
4. Selection phase : No major pelvic involvement: pelvic nodes ≤15 mm on CT scan
5. Selection phase : No distant metastasis
6. Selection phase : Patient unfit for radical cystectomy because of age, comorbidities, or patient’s refusal
7. Selection phase : Patients ≥18 years old
8. Selection phase : ECOG performance status ≤2
9. Selection phase : Life expectancy ≥12 months
10. Selection phase : 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: 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.
11. Selection phase : 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. Selection phase : Patients having provided written informed consent prior to any study-related procedures.
13. Selection phase : Patients affiliated to the social security scheme.
14. Selection phase : Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.
15. Inclusion phase : Patients who have received standard (chemo)-radiotherapy ≥60Gy or equivalent on the bladder according to the local practice.
16. Inclusion phase : The first administration of atezolizumab must be performed within 30 (+/-5) days after the last session of RT.
17. Inclusion phase : ECOG performance status ≤2.
18. Inclusion phase : 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; Adequate cardiac function: Troponin and CPK-MB at normal range.
19. Inclusion phase : 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.
20. Inclusion phase : Patients having provided written informed consent prior to any study-related procedures.
21. Inclusion phase : Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests, and other study procedures indicated in the protocol.

Exclusion criteria 18

1. Selection phase : Patient with bladder carcinoma in situ (CIS).
2. Selection phase : Known hypersensitivity to Chinese hamster ovary (CHO) cell products or any component of the atezolizumab formulation.
3. Selection phase : Prior allogeneic stem cell or solid organ transplant.
4. Selection phase : 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.
5. Selection phase : Patients with any other disease or illness which requires hospitalisation or is incompatible with the study treatment are not eligible.
6. Selection phase : 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.
7. Selection phase : Patients enrolled in another therapeutic study within 30 days of selection.
8. Selection phase : Pregnant or breast feeding women.
9. Selection phase : Person deprived of their liberty or under protective custody or guardianship.
10. Inclusion phase : In addition to the same non-inclusion criteria of selection phase that have to be respected, patients who have previously experienced a severe cutaneous reaction during previous treatment with an immune-stimulating anti-cancer agent.
11. Selection phase : Prior pelvic irradiation.
12. Selection phase : MIBC histology other than urothelial or squamous cell carcinomas (e.g., adenocarcinomas, micropapillary, sarcomas, or small cell histological types).
13. Selection phase : 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.
14. Selection phase : 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.
15. Selection phase : Contraindications for pelvic radiotherapy (e.g., inflammatory bowel disease).
16. Selection phase : History of immunodeficiency, including HIV infection, or systemic steroid therapy for any other disease.
17. Selection phase : A history of active autoimmune disease, except autoimmune-related hypothyroidism and type I diabetes mellitus
18. Selection phase : History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival (DFS) will be assessed at 2 years. DFS is defined as the delay between date of inclusion, and tumour progression (local, regional, or distant) or death of any cause, whichever occurs first.

Secondary endpoints 5

1. Local control rate will be evaluated by cystoscopy at 2 and 5 years. The presence of nonmuscle- 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. Duration of local control will be calculated from the date of inclusion till the date of positive cystoscopy. In case of regional or distant relapse occurring before local relapse, data will be censored at the time of relapse.
2. Disease-free survival (DFS) will be assessed at 5 years. DFS is defined as the delay between date of inclusion, and tumour progression (local, regional, or distant) or death of any cause, whichever occurs first.
3. Overall Survival (OS) will be assessed at 2 and 5 years. OS is defined as the delay between the date of inclusion and the date of death, of any cause.
4. The tolerance and safety will be evaluated by toxicity: acute (<6 months after the start of treatment) and late (≥6 months after the start of treatment), assessed using the NCI CTCAE v5.0 (see Appendix 2). The tolerance will be evaluated up until 5 years.
5. Quality of life

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications