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Phase 1

• Conditions: High-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of the bladder (TURBT) and pathological assessment.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004512-19-FR
• Lead Sponsor: ICANCER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-07-13
• Last Update Posted: 6 November 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 614

Inclusion Criteria

1. Signed informed consent form
2. Adult man and women ( age = 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 (G3) 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 case of T1 tumors, or incomplete initial TURB, or in case of doubt about completeness of a TURB, or if there is no muscle in the specimen (can be omitted if TaLG/G1 tumors or primary CIS only was found) without upstaging towards MIBC (EAU guidelines, 2017)
6. Absence of metastasis, as confirmed by a negative baseline computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pelvis, abdomen, and chest no more than 42 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 = 1500 cells/µL
- WBC counts > 2500/µL
- Lymphocyte count = 300/µL
- Platelet count = 100,000/µL
- Hemoglobin = 9.0 g/dL
- ASAT, ALAT, and alkaline phosphatase = 2.5 × the upper limit of normal (ULN)
- Serum bilirubin = 1.0 ×ULN
- Patients with known Gilbert disease who have serum bilirubin level = 3 × ULN may be enrolled.
- Partial thromboplastin time (PTT)/Prothrombin Time (PT) = 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 307
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 307

Exclusion Criteria

1. Patient having received previous BCG therapy for bladder cancer
2. Any approved anti-cancer therapy, including 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 except the following:
- Patients with localized low risk prostate cancer (defined as Stage =T2b, Gleason score = 7, and PSA at prostate cancer diagnosis = 20 ng/mL [if measured]) treated with curative intent and without prostate-specific antigen (PSA) recurrence are eligible.
- Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score = 7 and PSA = 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
- Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death <5% at 5 years) are eligible provided they meet all of the following criteria: malignancy treated with expected curative intent (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) and no evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers.
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 (see Appendix 7 for a more comprehensive list of autoimmune diseases)
- Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
- Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan may be eligible.
- History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
9. Serum albumin < 2.5 g/dL
10. Known HIV infection
11. Patients with known active hepatitis B virus (HBV; chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
- Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBc Ab] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomization.
- Patients positive for hepatitis C virus (HCV) antibody ar

Study & Design

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