A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy.

JRCT ID: jRCT2031210016

Registered date:06/04/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: ctDNA positive high risk MIBC
• Date of first enrollment: 06/09/2021
• Target sample size: 495
• Countries of recruitment: United States,Japan,Belgium,Japan,Canada,Japan,China,Japan,Czechia,Japan,France,Japan,Greece,Japan,Israe,Japan,South Korea,Japan,Poland,Japan,Russian,Japan,Spain,Japan,Ukraine,Japan,United Kingdom,Japan
• Study type: Interventional
• Intervention(s): atezolizumab: 1680 mg administered Intravenously (i. v.) once every 4 weeks for 12 cycles or 1 year

Outcome(s)

Primary Outcome

Efficacy
-Disease free survival

Secondary Outcome

Safety, Efficacy, Phamacokinetics, Other
-Overall survival
-Disease-Specific Survival
-Distant Metastasis-Free Survival
-Percentage of Participants With Adverse Events
-Patient-reported outcome (QOL)
-Pharmacokinetics

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Inclusion Criteria for the Surveillance Phase:
- Histologically confirmed MIUC (also termed TCC) of the bladder
- TNM classification at pathological examination of surgical resection specimen as follows:
For patients treated with prior NAC: tumor stage of ypT2-4a or ypN+ and M0.
For patients who have not received prior NAC: tumor stage of pT2-4a or pN+ and M0
- Surgical resection of MIUC of the bladder
- Patients who have not received prior platinum-based NAC, have refused, or are ineligible ("unfit") for cisplatin-based adjuvant chemotherapy
- Tumor PD-L1 expression per IHC and confirmed diagnosis of MIUC as documented through central testing of a representative tumor tissue specimen
- ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood
- Absence of residual disease and 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 4 weeks prior to enrollment.
- Full recovery from cystectomy and enrollment within 24 weeks following cystectomy

Additional Inclusion Criteria for the Treatment Phase:
- Plasma sample evaluated to be ctDNA positive
- Absence of residual disease and absence of metastasis, as confirmed by a negative baseline CT or MRI scan of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization.
- ECOG Performance Status of <= 2
- Adequate hematologic and end-organ function
- Life expectancy >=12 weeks
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs

Exclude criteria

General Medical Exclusion Criteria:
- Pregnancy or breastfeeding
- Positive test for HIV
- Patients with active hepatitis B virus or hepatitis C
- Active tuberculosis
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- History of autoimmune disease. 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, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- Significant cardiovascular disease, myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
- Known PD-L1 IHC result for adjuvant therapy.

Cancer-Specific Exclusion Criteria:
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment
-Adjuvant chemotherapy or radiation therapy for UC following cystectomy
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to enrollment
- Malignancies other than UC within 5 years prior to study enrollment

Additional Exclusion Criteria for the Treatment Phase:
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to randomization to the treatment phase Hormone-replacement therapy or oral contraceptives are allowed.
- Adjuvant chemotherapy or radiation therapy for UC following cystectomy
- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization to the treatment phase
- Positive test for HIV
- Patients with active hepatitis B virus or hepatitis C
- Active tuberculosis

Related Information

• Primary Sponsor: Hajer Lassidi
• Secondary ID(s): NCT04660344