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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42556   clinical trials with a EudraCT protocol, of which   7007   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2013-002616-28
    Sponsor's Protocol Code Number:N13NDT
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2013-09-24
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2013-002616-28
    A.3Full title of the trial
    Cytoreductive treatment of dabrafenib combined with trametinib to allow complete surgical resection in patients with BRAF mutated, prior unresectable stage III or IV melanoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial with patients who have a tumor that is too big to resect via operation, to treat them with systemic treatment to downsize the tumor, so that after 8 weeks the tumor can be resected and the patient is cured.
    A.3.2Name or abbreviated title of the trial where available
    Presurgical MAPK inhibition in stage III-IV melanoma
    A.4.1Sponsor's protocol code numberN13NDT
    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 SponsorNKI-AVL
    B.1.3.4CountryNetherlands
    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 supportGlaxoSmithKline
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNKI-AVL
    B.5.2Functional name of contact pointCRA
    B.5.3 Address:
    B.5.3.1Street AddressPlesmanlaan 121
    B.5.3.2Town/ cityAmsterdam
    B.5.3.3Post code1066CX
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31205122667
    B.5.5Fax number+31205122679
    B.5.6E-maill.pronk@nki.nl
    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 namedabrafenib
    D.3.2Product code GSK2118436
    D.3.4Pharmaceutical form Capsule
    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 INNDabrafenib
    D.3.9.1CAS number 1195765-45-7
    D.3.9.2Current sponsor codeGSK2118436
    D.3.9.3Other descriptive nameDABRAFENIB
    D.3.9.4EV Substance CodeSUB45696
    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 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) Yes
    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 nametrametinib
    D.3.2Product code GSK1120212
    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 INNTRAMETINIB
    D.3.9.2Current sponsor codeGSK1120212
    D.3.9.3Other descriptive nameTrametinib
    D.3.9.4EV Substance CodeSUB119776
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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) Yes
    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
    unresectable stage III/IV melanoma
    E.1.1.1Medical condition in easily understood language
    skin cancer that has spread out through the body
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level HLT
    E.1.2Classification code 10027156
    E.1.2Term Skin melanomas (excl ocular)
    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
    Primary objectives: To assess the ability of dabrafenib + trametinib treatment to downsize melanoma tumor masses to enable R0-resection.

    E.2.2Secondary objectives of the trial
    Secondary objectives: Recurrence free survival; time-to-next treatment, overall survival.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Objectives translational research:
    To investigate treatment induced changes in exome mutations within the tumor, changes in gene expression profiles and development of gene signatures for response to treatment, target protein inhibition (levels of pMEK, pERK, pAKT) and IHC for lymphocytic infiltrates and expression of PD-L1, Gata-3, IDO etc.)
    To perform patient derived xenografting (PDX) in immunodeficient mice to investigate development of resistance.
    E.3Principal inclusion criteria
    1. Patients have provided signed informed consent.
    2. Patients have unresectabel stage III melanoma (documented and based on MSD) or stage IV melanoma with ≤ 3 resectable metastases/organ site.
    3. Patients have pathologically confirmed BRAF mutation-positive (V600E/K) melanoma as determined via in-house testing with a BRAF mutation assay.
    4. Patients are treatment naïve for unresectable melanoma.
    5. Patients for whom the intended operation is considered to offer a chance of cure or substantial palliation.
    6. Patients have evaluable disease by CT/MRI or PET with ≤ 3 metastases/organ sites.
    7. Patients are ≥18 years of age.
    8. Patients are able to swallow and retain oral medication.
    9. Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.
    10. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment.
    11. Patients have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
    12. Patients must have adequate organ function as defined in the protocol. Treatment with transfusion, growth factors to meet eligibility criteria will not be allowed.
    E.4Principal exclusion criteria
    1. Patients with known ocular or primary mucosal melanoma.
    2. Patients who used any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of dabrafenib + trametinib.
    3. Patients who currently use a prohibited medication or are expected to require any of these medications during treatment with dabrafenib and trametinib.
    4. Patients who had any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.
    5. Patients with active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs.
    6. Patients with a history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
    7. Patients with a history of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
    8. Patients with a history of alcohol or drug abuse within 6 months prior to screening.
    9. Patients with psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, or unwillingness or inability to follow the procedures required in the protocol.
    10. Patients with the cardiac abnormalities as defined in the protocol.
    11. Pregnant or lactating female.
    12. Patients with CNS metastases.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is the % of patients in whom an R0-resection could be performed. This is measured by the pathologist, who handles the resection material (no positive margins) and negative CT-scans. Patients that develop a CR on systemic treatment will of course be included in the analysis. The aim of the study is to enable R0 resection.
    E.5.1.1Timepoint(s) of evaluation of this end point
    8 weeks after start study treatment.
    E.5.2Secondary end point(s)
    As the secondary endpoint recurrence-free survival will be assessed every 3 months by physical exam and CT-scan for 2 years, thereafter every 6 months for 2 year, and once in year 5. Thereafter by physical exam only. This will be assessed only in patients that undergo radical surgery. For patients not undergoing surgery, PFS will be assessed.
    Time to next treatment is defined as the moment the study treatment starts until start of any following treatment (surgery, RT or systemic treatment) for new lesions. This will be measured in all patients, but patients will be stratified for undergoing surgery or not undergoing surgery. Overall survival will be measured using Kaplan-Meier estimation for the total group of patients as well, again stratified for patients undergoing surgery or no surgery.
    E.5.2.1Timepoint(s) of evaluation of this end point
    During follow-up of the patient.
    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 Yes
    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.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    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
    It is a two-stage design. If the response in the first 14 patients is sufficient, than another 11 will be treated. The end of trial could be LVLS of the first stage (14 patients), or LVLS of the second stage (25 patients).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned 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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 state25
    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)
    The patient will be treated with dabrafenib and trametinib until PD.
    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 Decision2013-09-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-12-04
    P. End of Trial
    P.End of Trial StatusOngoing
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