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    The EU Clinical Trials Register currently displays   35177   clinical trials with a EudraCT protocol, of which   5751   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2015-001112-35
    Sponsor's Protocol Code Number:010463QM
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-09-17
    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 ConcernedUK - MHRA
    A.2EudraCT number2015-001112-35
    A.3Full title of the trial
    A phase II study investigating preoperative MPDL3280A in operable transitional cell carcinoma of the bladder
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II study investigating use of the drug MPDL3280A before surgery in bladder cancer patients
    A.3.2Name or abbreviated title of the trial where available
    ABACUS
    A.4.1Sponsor's protocol code number010463QM
    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 SponsorQueen Mary University of London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationQueen Mary University of London
    B.5.2Functional name of contact pointSally Burtles
    B.5.3 Address:
    B.5.3.1Street AddressJoint Research Management Office (JRMO), Queen Mary Innovation Centre, 5 Walden St.
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeE1 2EF
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02078827260
    B.5.6E-mailsponsorsrep@bartshealth.nhs.uk
    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 No
    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 nameMPDL3280A
    D.3.2Product code RO5541267
    D.3.4Pharmaceutical form 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 INNMPDL3280A
    D.3.9.3Other descriptive nameRO5541267
    D.3.9.4EV Substance CodeAS1
    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 No
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    T2-T4N0M0 transitional cell carcinoma of the bladder
    E.1.1.1Medical condition in easily understood language
    Bladder cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10066752
    E.1.2Term Bladder transitional cell carcinoma stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10066754
    E.1.2Term Bladder transitional cell carcinoma stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10066753
    E.1.2Term Bladder transitional cell carcinoma stage II
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine MPDL3280A's ability to reduce the size of bladder cancer before surgery (measured as pathological complete response rate), and assess the impact of the drug on the body's immune system.
    E.2.2Secondary objectives of the trial
    The secondary objectives are as follows:
    - Assess the safety and tolerability of MPDL3280A in this patient population by collecting information about adverse events and surgical complications.
    - Assess the anti-tumour effect of MPDL3280A by examining the radiological response (looking at pre- and post-treatment MRI/CT scan images) and “disease free survival” rates.
    - Assess the effect of MPDL3280A on overall patient survival.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Willing and able to provide written informed consent
    -Ability to comply with the protocol
    -Age ≥ 18 years
    -Histopathologically confirmed transitional cell carcinoma (T2-T4a) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern.
    -Residual disease after TURBT (surgical opinion, cystoscopy or radiological presence).
    -Fit and planned for cystectomy (according to local guidelines).
    -N0 or M0 disease CT or MRI (within 4 weeks of registration)
    -Representative formalin-fixed paraffin embedded (FFPE) bladder tumour samples with an associated pathology report that are determined to be available and sufficient for central testing.
    -Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is not appropriate.
    -Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
    -Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
    -For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 90 days after the last dose of MPDL3280A.
    -Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment defined by the following:
    a) ANC ≥ 1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
    b) WBC counts > 2500/μL
    c)Lymphocyte count ≥ 500/μL
    d) Platelet count ≥ 100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
    e) Haemoglobin ≥ 9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion).
    f) AST or ALT, and alkaline phosphatase ≤ 2.5 times the institutional upper limit of normal (ULN) (patients with known Gilbert disease who have serum bilirubin level ≤ 3 × the institutional ULN may be enrolled).
    g) INR and aPTT ≤ 1.5 × the institutional ULN. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
    h) Calculated creatinine clearance ≥ 20 mL/min (Cockcroft-Gault formula)
    E.4Principal exclusion criteria
    -Pregnant and lactating female patients
    -Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
    -Previous intravenous chemotherapy for bladder cancer
    -Patients with prior allogeneic stem cell or solid organ transplantation
    -Prior treatment with CD137 agonists, anti-CTLA-4, anti−programmed death−1 (PD-1), or anti−PD-L1 therapeutic antibody or pathway-targeting agents
    -Patients must not have had oral/IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids and mineralocorticoids is allowed.
    -Received therapeutic oral or intravenous antibiotics within 2 weeks prior to enrolment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
    -Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study
    -Treatment with systemic immunostimulatory agents (e.g. interferons or interleukin [IL]−2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment
    -Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment
    -Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
    -Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (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) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive)
    -Severe infections within 4 weeks prior to enrolment in the study (e.g. hospitalization for complications of infection, bacteraemia, severe pneumonia)
    -Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina
    -History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted)
    -Patients with uncontrolled Type 1 diabetes mellitus. Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible.
    -Patients with active hepatitis infection (positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
    -Positive test for HIV
    -Patients with active tuberculosis
    -History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
    -Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > the institutional ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients receiving denosumab prior to enrollment must be willing and eligible to receive bisphosphonate instead while on study
    -History of autoimmune disease including 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, glomerulonephritis
    -Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone
    -History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    -Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation
    E.5 End points
    E.5.1Primary end point(s)
    Clinical: Pathological complete response rate (pCRR) defined as ≥20% decrease in residual disease of the bladder, based on histological evaluation of the resected bladder specimen collected during cystectomy (post–treatment).

    Biological: Dynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre- and post-treatment with MPDL3280A.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Clinical: pCR rate will be based on histological evaluation of the resected bladder specimen collected during cystectomy (after 1-2 cycles of MPDL3280A treatment).

    Biological: The change in T cell expression will be measured in tumour biopsy samples collected before and after treatment with MPDL3280A (an archival sample and a sample taken at cystectomy or post- treatment biopsy).
    E.5.2Secondary end point(s)
    • Incidence, nature and severity of adverse events graded according to NCI-CTCAE v4.03 collected during and after MPDL3280A treatment.
    • Surgical complications as assessed by the Clavien-Dindo scoring system.
    • Radiological response, defined as a >30% decrease in tumour diameter from the baseline scan based on local investigator assessments
    • Disease-free survival, defined as time between the date of enrolment to first evidence of disease progression based on local investigator assessments or death, whichever occurs first.
    • Overall survival, defined as the time between the date of enrolment and death due to any cause.
    E.5.2.1Timepoint(s) of evaluation of this end point
    • Adverse events will be recorded during treatment and up to 24 weeks post cystectomy (AEs are recorded up to 4 weeks post-cystectomy, and unresolved AEs monitored until resolved or until 24 weeks post-cystectomy). Surgical complications will be assessed by the Clavien-Dindo scoring system post-cystectomy.
    • Radiological response will be assessed before and after treatment with MPDL3280A (baseline and pre-cystectomy).
    • Disease free survival will be recorded from enrolment until first evidence of disease recurrence or death; patients are followed up for 2 years after cystectomy.
    • Overall survival is defined as time from enrolment to death due to any cause. Patients are followed for 2 years after cystectomy; data will be collected until this time point.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA28
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 55
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 85
    F.4.2.2In the whole clinical trial 85
    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)
    None, this is a window of opportunity trial. On completion of the study, participating patients will be considered for further treatment at the discretion of the treating physician. MPDL3280A is still in development and is not available outside the clinical trial setting.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-11-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-16
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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