Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2016-004398-41
    Sponsor's Protocol Code Number:IJB-BC-TDM1BM-2016
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2017-12-06
    Trial results View 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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2016-004398-41
    A.3Full title of the trial
    Multicentre, non-randomised, open-label, single agent phase II study to determine the clinical benefit of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer patients with brain metastasis
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Multicentre, non-randomised, open-label, single agent phase II study to determine the clinical benefit of trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer patients with brain metastasis
    A.3.2Name or abbreviated title of the trial where available
    KIARA
    A.4.1Sponsor's protocol code numberIJB-BC-TDM1BM-2016
    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 SponsorInstitut Jules Bordet
    B.1.3.4CountryBelgium
    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.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationInstitut Jules Bordet
    B.5.2Functional name of contact pointCTSU
    B.5.3 Address:
    B.5.3.1Street AddressBoulevar de Waterloo 121
    B.5.3.2Town/ cityBruxelles
    B.5.3.3Post code1000
    B.5.3.4CountryBelgium
    B.5.6E-mailkiara@bordet.be
    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.2.5The 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 nameKadcycla
    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 INNTrastuzumab emtansine
    D.3.9.1CAS number 1018448-65-1
    D.3.9.3Other descriptive nameTRASTUZUMAB EMTANSINE
    D.3.9.4EV Substance CodeSUB35467
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metastatic HER2-positive breast cancer with brain metastasis
    E.1.1.1Medical condition in easily understood language
    Metastatic HER2-positive breast cancer with brain metastasis
    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 PT
    E.1.2Classification code 10065430
    E.1.2Term HER-2 positive breast cancer
    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 20.0
    E.1.2Level LLT
    E.1.2Classification code 10027475
    E.1.2Term Metastatic breast cancer
    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
    The primary objective of this study is to evaluate the Clinical Benefit Rate (CBR) of T-DM1 in brain lesions of patients with HER2-positive breast cancer with brain metastasis according to RECIST 1.1 as determined by local investigators
    E.2.2Secondary objectives of the trial
    This study has the following secondary objectives:
    1. To evaluate the CBR in brain lesions of patients with HER2-positive breast cancer with brain metastasis according to RECIST 1.1 as determined by central review;
    2. To evaluate the CBR in brain lesions of patients with HER2-positive breast cancer with brain metastasis according to RANO criteria as determined by local investigators;
    3. To evaluate the safety and cardiac-specific safety of the agent T-DM1;
    4. To evaluate the following efficacy parameters, in brain and systemic and bi-compartmental (as applicable) according to RANO criteria and RECIST 1.1: CBR, Overall Response Rate (ORR), Best Response (BR), PFS, DoR, Duration of Clinical Benefit (DCB)
    5. To evaluate the Overall Survival (OS) of this specific population;
    6. To assess the quality of life via multiple validated tools (EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20)).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Female patients (≥ 18 years);
    2. Histologically confirmed HER2-positive metastatic breast cancer patients (IHC 3+ and/or ISH positive) according to ASCO guidelines for HER2 testing49;
    3. Patients should have previously received trastuzumab and a taxane, separately or in combination. Patients should have either received prior therapy for locally advanced or metastatic disease, or developed disease recurrence during or within six months of completing adjuvant therapy;
    4. At least one measurable brain metastasis as defined by RECIST 1.1 (≥ 10 mm);
    5. Any hormone receptor status;
    6. Predicted life expectancy > 3 months;
    7. Any previous anti-HER2 therapies are allowed, other than T-DM1;
    8. ECOG performance score 0-2;
    9. No significant cardiac history and a current LVEF ≥ 50%. LVEF should be determined within 21 days before enrolment;
    10. Adequate organ function, evidenced by the following laboratory results. These are to be performed at a maximum of 7 days before enrolment:
    Absolute neutrophil count > 1,500 cells/mm3 without growth factor support (14 days after last peg-filgrastim, 7 days for regular filgrastim),
    Platelet count > 100,000 cells/mm3 without transfusion 2 weeks prior assessment,
    Hemoglobin > 9 g/dL without transfusion 2 weeks prior assessment, Aspartate aminotransferase and alanine aminotransferase < 2.5 x upper limit of normal (ULN),
    Total bilirubin ≤ 1.5 x ULN unless the patient has documented Gilbert’s syndrome, in which case direct (conjugated) bilirubin level needs to be within normal limits,
    Serum alkaline phosphatase ≤ 2.5 x ULN. Patients with bone metastases: alkaline phosphatase ≤ 5 x ULN,
    Serum creatinine < 2.0 mg/dL or < 177 μmol/L,
    International normalized ratio and activated partial thromboplastin time or partial thromboplastin time < 1.5 ULN unless patient receiving anticoagulant therapy;
    11. For women of childbearing potential a serum pregnancy test will be done up to 7 days before enrolment (and it must be negative) and an agreement to use one highly-effective form of non-hormonal contraception (true abstinence, vasectomy,oophorectomy, /hysterectomy, IUD) or two effective forms of non-hormonal contraception (e.g., condoms plus spermicidal agent) at study entry (to be put in place within 2 weeks prior to enrolment), during the administration of T-DM1 and for 7 months after the last administration of T-DM1 will be obtained;
    12. Signed informed consent obtained before any study-specific procedure;
    13. Able and willing to comply with the protocol; including the willingness to provide samples (primary if available and blood) for translational research.
    Cohort 1 Specific Criteria:
    14. No corticosteroids at enrolment for metastasis related symptoms (low dose (max 4mg dexamethasone or equivalent per day due to other comorbidities is acceptable)
    15. Oligosymptomatic (defined as not requiring immediate intervention for symptom control) or asymptomatic brain metastases not requiring immediate local therapy.
    Cohort 2 Specific Criteria:
    16. Radiologically confirmed brain progression after previous local therapy (neurosurgery, radiosurgery to the brain, stereotactic radiotherapy to the brain, or whole brain radiotherapy) with at least 3 months between end of local therapy and brain progression.
    17. Decreasing corticosteroid dose or stable dose for at least one week prior to enrolment
    E.4Principal exclusion criteria
    1. Single brain metastasis with indication of surgical resection;
    2. Pregnant or breast-feeding women;
    3. Documented leptomeningeal disease;
    4. Having received any investigational therapy within ≤ 28 days or 5 half-lives prior to enrolment, whichever is longer;
    5. Having received hormonal therapy within 14 days prior to enrolment;
    6. Having received trastuzumab within 21 days prior to enrolment;
    7. History of treatment with trastuzumab emtansine;
    8. Prior enrolment in a T-DM1containing study, regardless of whether the patient received T-DM1 or not;
    9. History of intolerance (including Grade 3 or 4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the investigational medicinal product;
    10. Current peripheral neuropathy of Grade ≥ 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.0.3;
    11. History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those mentioned above;
    12. Current unstable ventricular arrhythmia requiring treatment;
    13. History of symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] Classes II−IV);History of myocardial infarction or unstable angina within 6 months prior to first study drug administration;
    15. Current dyspnoea at rest due to complications of advanced malignancy or currently requiring continuous oxygen therapy;
    16. Current severe, uncontrolled disease other than cancer (e.g., clinically significant pulmonary, hypertension or metabolic disease, among others);
    17. Concurrent, serious, uncontrolled infections or current known infection with HIV, active hepatitis B and/or hepatitis C;
    18. Major surgical procedure or significant traumatic injury within 28 days before enrolment or anticipation of the need for major surgery during the course of study treatment;
    19. Known contraindications for undergoing MRI or CT, including receiving contrast media.
    Cohort 1 : Additional Specific Criteria
    20. Previous neurosurgery or radiotherapy (including radiosurgery, stereotactic radiotherapy. or whole brain radiotherapy) to the brain.
    Cohort 2 : Additional Specific Criteria
    There are none.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is the CB at first radiological assessment (after 3 cycles or earlier if clinically indicated), defined as complete response plus partial response plus stable disease in the brain, as measured by RECIST 1.1 and as determined by local investigators.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at first radiological assessment
    E.5.2Secondary end point(s)
    The secondary endpoints of this study are:
    1. CB in the brain as measured by RECIST 1.1 (see appendix 1), as determined by central review;
    2. CB in the brain measured by RANO (see appendix 2) brain metastases criteria, as determined by local investigators;
    3. General and cardiac-specific safety;
    Incidence, type and severity of all adverse events (AEs) and serious adverse events (SAEs) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03);
    Incidence and type of AEs leading to discontinuation, modification, or delay of T-DM1 dose;
    4. The following additional efficacy parameters. All of them will be determined both by RANO and RECIST 1.1:
    CB: Systemic and bi-compartmental (see definition above),
    Overall Response (OR): defined as complete response plus partial response in: (1) brain, (2) systemically, (3) bi-compartmentally,
    Best Response (BR): in the brain, systemic and bi-compartmental defined as the best obtained response (be it PD, SD, PR or CR), among all imaging assessments,
    PFS: PFS defined as time between enrolment in the study and progression (systemic, brain and bi-compartmental) or death,
    DoR: defined as time from documentation of tumour response to in the brain (PR or CR) disease progression in the brain; systemic defined as time from documentation of non-brain tumour response (PR or CR) to non-brain progression, Bi-compartmental defined as time between response and progression,
    Duration of Clinical Benefit (DCB): is defined as the time elapsed between determination of SD, PR or CR and determination of disease progression;
    5. OS defined as time between enrolment in the study and death
    6. Quality of life (QoL).
    E.5.2.1Timepoint(s) of evaluation of this end point
    As per protocol.
    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 No
    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 Yes
    E.8.1.7.1Other trial design description
    single arm, two distinct cohorts of patients
    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.8.3 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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 No
    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 last patient last visit (LPLV) at the end of the follow-up period. This will be the last data collection point, which can be a clinic visit, a laboratory sample or checking of record/telephone contact for determination of OS. LPLV is expected to occur approximately 18 months after the last patient has been enrolled in the study.
    AND
    The database has been fully cleaned and frozen for all analyses.
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    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: 80
    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 No
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 0
    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)
    At the discretion of the physician according to the national standard practice
    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 Decision2017-11-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-26
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 04:29:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA