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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2020-004418-36
    Sponsor's Protocol Code Number:BO42843
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-02-18
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2020-004418-36
    A.3Full title of the trial
    A PHASE III, DOUBLE-BLIND, MULTICENTER, RANDOMIZED STUDY OF ATEZOLIZUMAB (ANTI-PD-L1 ANTIBODY) VERSUS PLACEBO AS
    ADJUVANT THERAPY IN PATIENTS WITH HIGH-RISK MUSCLE-INVASIVE BLADDER CANCER WHO ARE CTDNA-POSITIVE FOLLOWING CYSTECTOMY
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate Effects of Atezolizumab (anti-PD-L1 antibody) as an Adjuvant Therapy in Patients with High-Risk Muscle-invasive Bladder Cancer
    A.4.1Sponsor's protocol code numberBO42843
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorF. Hoffmann-La Roche Ltd.
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF.Hoffmann-La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+4161 688 1111
    B.5.5Fax number+4161 691 9319
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tecentriq
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAtezolizumab
    D.3.2Product code RO5541267/F05
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNATEZOLIZUMAB
    D.3.9.1CAS number 1380723-44-3
    D.3.9.2Current sponsor codeRO5541267
    D.3.9.3Other descriptive nameMPDL3280A, Tecentriq
    D.3.9.4EV Substance CodeSUB178312
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboConcentrate for solution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    muscle-invasive urothelial carcinoma (also termed transitional cell carcinoma [TCC]) of the bladder
    E.1.1.1Medical condition in easily understood language
    high-risk muscle-invasive bladder cancer (MIBC)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10046714
    E.1.2Term Urothelial carcinoma bladder
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    •To evaluate the efficacy of atezolizumab compared with placebo on basis of Independent Review Facility (IRF)-assessed disease-free survival (DFS) in patients who are circulating-tumor DNA (ctDNA)-positive within 20 weeks of cystectomy (primary analysis population)
    E.2.2Secondary objectives of the trial
    •To evaluate the efficacy of atezolizumab compared with placebo on the basis of overall survival (OS), IRF- assessed DFS (randomized population), investigator assessed DFS (primary analysis and randomized population), disease-specific survival (DSS), distant metastasis-free survival (DMFS), quality of life (QoL) and ctDNA clearance
    •To evaluate the safety of atezolizumab compared with placebo
    •To characterize the pharmacokinetic (PK) profile of atezolizumab
    •To evaluate the immune response to atezolizumab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    •Age >=18 years at time of signing Informed Consent Form
    •Histologically confirmed muscle-invasive urothelial carcinoma (MIUC) (also termed transitional cell carcinoma [TCC]) of the bladder
    •TNM classification (based on American Joint Committee on Cancer [AJCC] Cancer Staging Manual, 7th Edition) at pathological examination of surgical resection
    – 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 neoadjuvant chemotherapy (NAC), have refused, or are ineligible (“unfit”) for cisplatin-based adjuvant chemotherapy
    •Availability of a surgical tumor specimen that is suitable (adequate quality and quantity) for use in determining ctDNA status and for exploratory biomarker research assessed by central laboratory testing
    •Tumor tissue specimen submitted within 10 weeks of cystectomy for ctDNA assay development
    •A post-surgery blood sample for the identification of somatic mutations in tumor tissue and for plasma preparation for determining ctDNA status must also be submitted for screening
    •ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood
    •Tumor PD-L1 expression per immunohistochemistry (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 (Minimum of 6 weeks must have elapsed from surgery)
    •If patient-reported outcome (PRO) data are collected via an electronic device, patients must be willing and able to use the device
    Additional Inclusion Criteria for the Treatment Phase
    •Plasma sample evaluated to be ctDNA-positive, defined as the presence of two or more mutations based on patient’s personalized ctDNA multiplex Polymerase Chain Reaction (mPCR) assay
    •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
    •Eastern Cooperative Oncology Group (ECOG) Performance Status of <=2
    •Life expectancy >=12 weeks
    •Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment
    •Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs during the treatment period and for 5 months after the final dose of atezolizumab
    E.4Principal 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, 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
    •History of idiopathic pulmonary fibrosis, organizing pneumonia (bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
    •Serum albumin <2.5 grams per deciliter (g/dL)
    •Positive test for human immunodeficiency virus (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
    •Prior allogeneic stem cell or solid organ transplant
    •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 may render the patient at high risk from treatment complications
    •Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to study enrollment or randomization to the treatment phase
    •Adjuvant chemotherapy or radiation therapy for urothelial carcinoma (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 or randomization to the treatment phase
    •Malignancies other than UC within 5 years prior to study enrollment
    •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
    •Receipt of therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to Cycle 1, Day 1
    •Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
    •Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
    •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
    •Treatment with systemic immunostimulatory agents (including, but not limited to, IFNs, IL-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
    •Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic immunosuppressive medications during the trial
    •Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
    E.5 End points
    E.5.1Primary end point(s)
    1. IRF-assessed DFS in patients who are ctDNA-positive within 20 weeks of cystectomy (primary analysis population)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Up to approximately 6 years
    E.5.2Secondary end point(s)
    1. OS in patients who are ctDNA-positive within 20 weeks after cystectomy (primary analysis population)
    2. IRF-assessed DFS in all randomized patients
    3. Investigator-assessed DFS in the primary analysis population
    4. Investigator-assessed DFS in all randomized patients
    5. Investigator-assessed DSS in the primary analysis population
    6. Investigator-assessed DMFS in the primary analysis population
    7. Time to deterioration of function and QoL in the primary analysis population and in the all randomized population
    8. ctDNA clearance in the primary analysis population
    9. Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
    10. Change from baseline in targeted vital signs
    11. Change from baseline in targeted clinical laboratory test results
    12. Serum concentration of atezolizumab at specified timepoints
    13. Incidence of anti-drug antibodies (ADAs) to atezolizumab during the study
    14. Prevalence of ADAs to atezolizumab at baseline
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-7. Up to approximately 6 years
    8. Baseline (Day-28 to Day-1), Day 1 of cycles 3 and 5
    9. Up to approximately 6 years
    10-11. Baseline to approximately 6 years
    12. Day 1 of Cycles 1, 2, 3, 4, 8, and 12
    13. Day 1 and 21 of Cycle 1, Day 1 of Cycles 2, 3, 4, 8, and 12
    14. At Baseline
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Surveillance phase
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA38
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Brazil
    Canada
    China
    Israel
    Japan
    Korea, Republic of
    Russian Federation
    Taiwan
    Turkey
    Ukraine
    United States
    Belgium
    France
    Germany
    Greece
    Italy
    Poland
    Spain
    United Kingdom
    Czechia
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of this study is defined as the date when the required number of events for the final analysis of OS in the primary analysis population has occurred. The end of the study is expected to occur approximately Month 73 from the time the first patient in the primary analysis population is randomized (see Section 6.2.3).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years8
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 198
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 297
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 461
    F.4.2.2In the whole clinical trial 495
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    There are no plans to provide treatment after the subject completes his/ her participation in the trial
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-02-26
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-03-09
    P. End of Trial
    P.End of Trial StatusOngoing
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