Clinical Trials /

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

NCT04660344

Description:

This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are ctDNA positive and are at high risk for recurrence following cystectomy.

Related Conditions:
  • Infiltrating Bladder Urothelial Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy
  • Official Title: A Phase III, Double-Blind, Multicenter, Randomized Study of Atezolizumab (Anti-PDL1 Antibody) Versus Placebo as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Bladder Cancer Who Are ctDNA Positive Following Cystectomy

Clinical Trial IDs

  • ORG STUDY ID: BO42843
  • NCT ID: NCT04660344

Conditions

  • Muscle-invasive Bladder Cancer

Interventions

DrugSynonymsArms
AtezolizumabTecentriqArm A: Atezolizumab

Purpose

This is a global Phase III, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab compared with placebo in participants with MIBC who are ctDNA positive and are at high risk for recurrence following cystectomy.

Trial Arms

NameTypeDescriptionInterventions
Arm A: AtezolizumabExperimentalAtezolizumab will be administered intravenously at a dose of 1680 milligrams (mg) on Day 1 of each 28-day cycle for 12 cycles or up to 1 year (whichever occurs first). Atezolizumab will be discontinued in the event of IRF-assessed disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.
  • Atezolizumab
Arm B: PlaceboPlacebo ComparatorPlacebo will be administered intravenously on Day 1 of each 28-day cycle. Placebo will be discontinued in the event of IRF-assessed disease recurrence, unacceptable toxicity, withdrawal of consent, or study termination by the Sponsor.

    Eligibility Criteria

            Inclusion Criteria for the Surveillance Phase:
    
              -  Histologically confirmed MIUC (also termed TCC) of the bladder
    
              -  TNM classification (based on AJCC Cancer Staging Manual, 7th Edition; Edge et al.
                 2010) 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 pT3-4a 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
    
              -  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 14 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
    
              -  Life expectancy >=12 weeks
    
              -  Adequate hematologic and end-organ function
    
              -  For women of childbearing potential: agreement to remain abstinent (refrain from
                 heterosexual intercourse) or use contraception and agreement to refrain from donating
                 eggs
    
            General Medical Exclusion Criteria:
    
              -  Pregnancy or breastfeeding
    
              -  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. History of radiation pneumonitis in the radiation field (fibrosis) is
                 permitted.
    
              -  Positive test for HIV
    
              -  Patients with active hepatitis B virus or hepatitis C
    
              -  Active tuberculosis
    
              -  Significant cardiovascular disease, such as New York Heart Association cardiac disease
                 (Class II or greater), myocardial infarction within the previous 3 months, unstable
                 arrhythmias, or unstable angina
    
            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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:IRF-assessed DFS in Participants Who Are ctDNA Positive Within 20 Weeks of Cystectomy
    Time Frame:Randomization up to first occurrence of DFS event (up to approximately 73 months)
    Safety Issue:
    Description:Independent Review Facility(IRF)-assessed disease-free survival (DFS) in participants who are ctDNA positive within 20 weeks of cystectomy (primary analysis population), defined as the time from randomization to the first occurrence of a DFS event, defined as any of the following: Local (pelvic) recurrence of urothelial carcinoma (UC) (including soft tissue and regional lymph nodes) Urinary tract recurrence of UC (including all pathological stages and grades) Distant metastasis of UC Death from any cause

    Secondary Outcome Measures

    Measure:Overall survival (OS) in Participants Who Are ctDNA Positive Within 20 weeks After Cystectomy
    Time Frame:Randomization up to death from any cause (up to approximately 73 months)
    Safety Issue:
    Description:Overall survival (OS) in participants who are ctDNA positive within 20 weeks after cystectomy (primary analysis population), defined as the time from randomization to death from any cause.
    Measure:IRF-assessed DFS in All Randomized Participants
    Time Frame:Randomization up to first occurrence of DFS event (up to approximately 73 months)
    Safety Issue:
    Description:
    Measure:Investigator-Assessed DFS in Primary Analysis Population
    Time Frame:Randomization up to first occurrence of DFS event (up to approximately 73 months)
    Safety Issue:
    Description:
    Measure:Investigator-Assessed DFS in All Randomized Participants
    Time Frame:Randomization up to first occurrence of DFS event (up to approximately 73 months)
    Safety Issue:
    Description:
    Measure:Investigator-Assessed Disease-Specific Survival in Primary Analysis Population
    Time Frame:Randomization to death from UC (up to approximately 73 months)
    Safety Issue:
    Description:Investigator-assessed disease-specific survival in the primary analysis population, defined as the time from randomization to death from UC per investigator assessment of cause of death.
    Measure:Investigator-Assessed Distant Metastasis-Free Survival in Primary Analysis Population
    Time Frame:Randomization to diagnosis of distant metastases or death from any cause (up to approximately 73 months)
    Safety Issue:
    Description:Investigator-assessed distant metastasis-free survival in the primary analysis population, defined as the time from randomization to the diagnosis of distant (i.e., non-locoregional) metastases or death from any cause.
    Measure:Time to Deterioration of Function and Quality of Life (QoL) in Primary Analysis Population and in All Randomized Population
    Time Frame:Randomization to participant's first score decrease of >=10 points from Baseline on EORTC QLQ-C30 physical function scale, role function scale, and the GHS/QoL Scale (up to approximately 73 months)
    Safety Issue:
    Description:Time to deterioration of function and quality of life (QoL) in the primary analysis population and in the all randomized population, defined as the time from randomization to the date of a participants's first score decrease of >= 10 points from baseline on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) physical function scale, role function scale, and the global health status (GHS)/QoL scale (separately).
    Measure:ctDNA Clearance in Primary Analysis Population
    Time Frame:Baseline, Cycle 3 Day 1 or Cycle 5 Day 1 (each cycle is 28 days)
    Safety Issue:
    Description:ctDNA clearance in the primary analysis population, defined as the proportion of patients who are ctDNA positive at baseline and ctDNA negative at Cycle 3, Day 1 or Cycle 5, Day 1.
    Measure:Percentage of Participants With Adverse Events
    Time Frame:Baseline up to approximately 73 months
    Safety Issue:
    Description:
    Measure:Serum Concentration of Atezolizumab
    Time Frame:At pre-defined intervals from first administration of study drug up to approximately 73 months
    Safety Issue:
    Description:
    Measure:Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab
    Time Frame:Baseline up to approximately 73 months
    Safety Issue:
    Description:Incidence of anti-drug antibodies (ADAs) to atezolizumab during the study.
    Measure:Prevalence of ADAs to Atezolizumab
    Time Frame:Baseline
    Safety Issue:
    Description:Prevalence of ADAs to atezolizumab at baseline.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Hoffmann-La Roche

    Last Updated

    December 23, 2020