Clinical trial evaluating the efficacy of the Atezolizumab (experimental treatment) in association to one year of standard treatment (BCG) in patient suffering from a bladder cancer which has not invaded the muscle but with high risk of relapse

Phase 1

• Conditions: High-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of the bladder (TURBT) and pathological assessment.; MedDRA version: 20.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004512-19-ES
• Lead Sponsor: nicancer

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 516

Inclusion Criteria

1. Signed informed consent form after the last endoscopic surgery (TURBT)
2. Adult man and women ( age > or= 18 years)
3. Any high risk non muscle invasive urothelial carcinoma histologically confirmed (mixed histology tumors allowed if urothelial carcinoma histology is predominant) defined on the TURBT as any of the following
T1 tumor and/or
High grade (WHO 2004) and/or
Grade 3 (WHO 1973) and/or
Carcinoma in situ (CIS)
4. Tumor tissue available from the surgery for central confirmation of the diagnosis and analysis the expression of PD-L1
5. At least one additional (second) resection of the primary tumor has been performed in any of the following cases [without upstaging toward MIBC (EAU guidelines, 2017)] :
- T1 tumors at physician’s discretion,
- incomplete initial TURBT,
- no muscle in the specimen (can be omitted if TaLG/G1 tumors or primary CIS only was found).
6. Absence of metastasis in the pelvis, abdomen, or chest, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan no more than 90 days prior to the first study treatment
7. ECOG performance status of = 2
8. Life expectancy = 12 weeks
9. Systolic blood pressure (BP) <160 mmHg and diastolic BP <95 mmHg, as documented within 7 days prior to the first study treatment (hypertension allowed provided it is controlled)
10. Adequate hematologic and end-organ function, as defined by the following laboratory results obtained within 7 days prior to the first study treatment:
ANC > or= 1500 cells/microL
WBC counts > 2500/microL
Lymphocyte count > or= 300/microL
Platelet count > or= 100,000/microL
Hemoglobin > or= 9.0 g/dL
ASAT, ALAT, and alkaline phosphatase = 2.5 × the upper limit of normal (ULN)
Serum bilirubin < or = 1.0 ×ULN
Patients with known Gilbert disease who have serum bilirubin level < or = 3 × ULN may be enrolled.
Partial thromboplastin time (PTT)/Prothrombin Time (PT) < or = 1.5 × ULN or INR < 1.7 × ULN
Calculated creatinine clearance = 20 mL/min (Cockcroft-Gault formula)
11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab
12. Patients affiliated to the social security system
13. Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 258
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 258

Exclusion Criteria

1. Patient having received previous BCG therapy for bladder cancer
2. Any approved anti-cancer therapy, including systemic chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment. Hormone-replacement therapy or oral contraceptives are allowed
3. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to day 1 of study treatment
4. Malignancies other than UC within 5 years prior to Day 1 of cycle 1 of treatment
5. Pregnancy or breastfeeding
6. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
7. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
8. History of autoimmune disease or history of immunosuppression, or conditions associated with congenital or acquired immune deficiency , including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
9. Serum albumin < 2.5 g/dL
10. Known HIV infection
11. Patients with active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test prior to randomization) or hepatitis C.
12. Known active tuberculosis
13. Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
14. Signs or symptoms of urinary infection and/or other signs and symptoms > grade 1 (NCI CTCAE v5.0) within 2 weeks prior to Cycle 1, Day 1.
Patients receiving therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 are not eligible. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
15. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months before Cycle 1, Day 1, unstable arrhythmias, or unstable angina.
16. Major surgical procedure other than for diagnosis within 4 weeks prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
17. Prior allogeneic stem cell or solid organ transplant
18. Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation if such a live, attenuated vaccine will be required during the study
19. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
20. Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
21. Treatment with systemic immunostimulatory agents (including but not limited to interferons, IL-2) within 6 weeks or five half-live

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified