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    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   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:2015-002801-12
    Sponsor's Protocol Code Number:ONT-380-206
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2017-03-09
    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 ConcernedGermany - BfArM
    A.2EudraCT number2015-002801-12
    A.3Full title of the trial
    Phase 2 Randomized, Double-Blinded, Controlled Study of Tucatinib vs. Placebo in Combination with Capecitabine and Trastuzumab in
    Patients with Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma (HER2CLIMB)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial comparing tucatinib against placebo in patients who have advanced breast cancer and are being treated with capecitabine and trastuzamab
    A.4.1Sponsor's protocol code numberONT-380-206
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02614794
    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 SponsorSeagen Inc.
    B.1.3.4CountryUnited States
    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 supportSeagen Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSeagen Trial Information Support
    B.5.2Functional name of contact pointSeagen Trial Information
    B.5.3 Address:
    B.5.3.1Street Address21823 30th Drive SE
    B.5.3.2Town/ cityBothell
    B.5.3.3Post codeWA 98021
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1866333 7436
    B.5.6E-mailclinicaltrials@seagen.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 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 nameTucatinib
    D.3.2Product code ONT-380
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTucatinib
    D.3.9.1CAS number 937263-43-9
    D.3.9.2Current sponsor codeONT-380
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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) No
    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.IMP: 2
    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 nameTucatinib
    D.3.2Product code ONT-380
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTucatinib
    D.3.9.1CAS number 937263-43-9
    D.3.9.2Current sponsor codeONT-380
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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) No
    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
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Carcinoma
    E.1.1.1Medical condition in easily understood language
    Breast cancer which may have spread
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10065430
    E.1.2Term HER2 positive 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
    To assess the effect of tucatinib vs. placebo in combination with capecitabine and trastuzumab on progression-free survival (PFS) per RECIST 1.1 based on blinded independent central review (BICR)
    E.2.2Secondary objectives of the trial
    Double-Blinded Phase:
    To assess the effect of tucatinib vs. placebo in combination with capecitabine and trastuzumab in patients with brain metastases at baseline using RECIST 1.1 based on BICR
    To assess the effects of tucatinib vs. placebo in combination with capecitabine and trastuzumab on OS
    To assess the health-related quality of life and health economics associated with tucatinib vs. placebo in combination with capecitabine and trastuzumab

    Safety Objective
    To assess the safety and tolerability of tucatinib in combination with capecitabine and trastuzumab

    Pharmacokinetic Objective
    To evaluate the pharmacokinetics of tucatinib and metabolite ONT-993 when administered in combination with capecitabine and trastuzumab


    Unblinded Phase:
    To assess the safety and tolerability of tucatinib in combination with capecitabine and trastuzumab
    To assess PFS per RECIST 1.1 by investigator
    To assess OS
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Double-Blinded Phase:
    Have histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) methodology

    Have received previous treatment with a taxane, trastuzumab, pertuzumab, and T-DM1

    Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy

    Have measurable or non-measureable disease assessable by RECIST 1.1

    At least 18 years of age at time of consent

    Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1

    Have adequate hepatic function

    Have adequate baseline hematologic parameters

    Have creatinine clearance ≥ 50 mL/min or, in patients ≤ 45 kg in weight, a serum creatinine within institutional normal limits

    Have left ventricular ejection fraction (LVEF) ≥ 50%

    If female of childbearing potential, must have a negative result of serum or urine pregnancy test.

    Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective birth control methods.

    CNS Inclusion – Based on screening contrast brain magnetic resonance imaging (MRI), patients must have one of the following:
    - No evidence of brain metastases
    - Untreated brain metastases not needing immediate local therapy.
    - Previously treated brain metastases
    a. Brain metastases previously treated with local therapy my either be stable since treatment or may have progressed since prior local CNS
    therapy.
    b. Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enrol if all of the following criteria are met:
    i. Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of treatment, or time since surgical resection is ≥ 28 days
    ii. Other sites of disease assessable by RECIST 1.1 are present
    c. Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions


    Unblinded Phase:
    For patients who were randomized to the control arm and on the longterm follow-up period at the time of the crossover screening: have
    progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy.

    Have measurable or non-measurable disease assessable by RECIST 1.1

    Have ECOG PS 0 or 1

    Adequate hepatic function

    Adequate hematologic parameters

    Have creatinine clearance ≥ 50 mL/min as calculated per institutional guidelines or, in patients ≤ 45 kg in weight, serum creatinine within
    institutional normal limits

    Have LVEF ≥ 50% as assessed by ECHO or MUGA scan documented within 6 weeks prior to the time of crossover consent

    If female of childbearing potential, must have a negative result of serum or urine pregnancy test.

    Women of childbearing potential and men with partners of childbearing potential must agree to use a highly effective birth control methods

    CNS Inclusion – Based on screening contrast brain magnetic resonance imaging (MRI), patients must have one of the following:
    - No evidence of brain metastases
    - Untreated brain metastases not needing immediate local therapy.
    - Previously treated brain metastases
    a. Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy.
    b. Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if all of the following criteria are met:
    i. Time since whole brain radiation therapy (WBRT) is ≥ 21 days prior to first dose of treatment, time since stereotactic radiosurgery (SRS) is ≥ 7 days prior to first dose of treatment, or time since surgical resection is ≥ 28 days
    ii. Other sites of disease assessable by RECIST 1.1 are present
    E.4Principal exclusion criteria
    Double-Blinded Phase:
    Have previously been treated with:
    a. lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity)
    b. neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) at any time previously.

    Have previously been treated with capecitabine (or other fluoropyrimidine [e.g., 5-fluorouracil]) for metastatic disease (except in cases where capecitabine was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity). Note patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.

    Have previously been treated with capecitabine for metastatic disease. Note patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible.

    Have any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1.

    Have clinically significant cardiopulmonary disease.

    Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease

    Are known to be positive for human immunodeficiency virus (HIV)

    Require therapy with warfarin or other coumarin derviatives

    Unable for any reason to undergo MRI of the brain

    CNS Exclusion – Based on screening brain MRI, patients must not have any of the following:
    Any untreated brain lesions > 2.0 cm in size unless discussed with medical monitor and approval for enrolment is given

    Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total dose of > 2mg dexamethasone.

    Any brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria 19b

    Known or suspected leptomeningeal disease (LMD)


    Unblinded Phase:
    Discontinuation of study treatment due to an adverse event while on the double-blind phase of the study

    Have any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1

    Have clinically significant cardiopulmonary disease

    Are known carriers of Hepatitis B or Hepatitis C or have other known chronic liver disease

    Are known to be positive for HIV

    Require therapy with warfarin or other coumarin derivatives

    Unable for any reason to undergo contrast MRI of the brain

    CNS Exclusion – Based on crossover screening brain MRI, patients must not have any of the following:
    Any untreated brain lesions > 2.0 cm in size unless discussed with medical monitor and approval for enrolment is given
    Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total dose of > 2mg dexamethasone.
    Any brain lesion thought to require immediate local therapy. Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria
    E.5 End points
    E.5.1Primary end point(s)
    Progression Free Survival
    E.5.1.1Timepoint(s) of evaluation of this end point
    Time from randomization to documented disease progression (as determined by BICR per RECIST 1.1), or death from any cause, whichever occurs first
    E.5.2Secondary end point(s)
    Efficacy
    - PFS in patients with brain metastases at baseline using RECIST 1.1, as determined by BICR
    - OS
    - Comparative health economics

    Safety
    - Adverse events (AEs)

    Pharmacokinetics
    - Plasma concentrations of tucatinib and metabolites
    E.5.2.1Timepoint(s) of evaluation of this end point
    Efficacy - Time from randomization to documented disease progression (as documented by BICR per RECIST 1.1), or death from any cause, whichever occurs first

    OS - End of the study

    Safety - Time from randomization to 30 days of last dose.
    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 Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    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 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 No
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA83
    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
    Canada
    Israel
    United States
    Switzerland
    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 years
    E.8.9.1In the Member State concerned months61
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months72
    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: 468
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 132
    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 state25
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 252
    F.4.2.2In the whole clinical trial 600
    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 time of study closure, patients will revert to physician care.
    When applicable, the Sponsor will assist with post-trial access to tucatinib.
    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 Decision2017-06-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-08-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-08-11
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