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    Summary
    EudraCT Number:2013-003452-21
    Sponsor's Protocol Code Number:BRF117277
    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:2014-01-07
    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 number2013-003452-21
    A.3Full title of the trial
    BRF117277: A Phase II, Open-Label, Multicentre Study of Dabrafenib plus Trametinib in Subjects with BRAF Mutation-Positive Melanoma that has Metastasized to the Brain
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Open-Labeled Study of Dabrafenib plus Trametinib in Subjects with BRAF Mutation-Positive Melanoma that has Metastasized to the Brain.
    A.4.1Sponsor's protocol code numberBRF117277
    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 SponsorNovartis Pharma Services AG
    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 supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharma Services AG
    B.5.2Functional name of contact pointClinical Trials Information Desk
    B.5.3 Address:
    B.5.3.1Street AddressForum 1 Novartis Campus
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4056
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+41613241111
    B.5.5Fax number+41613248001
    B.5.6E-mailclinicaltrial.enquiries@novartis.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 Tafinlar
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline trading Services Ltd.
    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 nameTafinlar
    D.3.2Product code GSK1218436
    D.3.4Pharmaceutical form Capsule, hard
    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 mesilate
    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 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.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 Yes
    D.2.1.1.1Trade name Tafinlar
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline trading Services Ltd.
    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 nameTafinlar
    D.3.2Product code GSK1218436
    D.3.4Pharmaceutical form Capsule, hard
    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 mesilate
    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 number75
    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: 3
    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 Film-coated 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 codeGSK1220212
    D.3.9.3Other descriptive nameN-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]- 6,8-dimethyl-2,4,7-trioxo-
    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 number0.5
    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: 4
    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 Film-coated 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 codeGSK1220212
    D.3.9.3Other descriptive nameN-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]- 6,8-dimethyl-2,4,7-trioxo-
    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 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Subjects with BRAF Mutation-Positive Melanoma that has Metastasized to the Brain
    E.1.1.1Medical condition in easily understood language
    Metastic Melanoma.
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10027481
    E.1.2Term Metastatic melanoma
    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 assess the intracranial response (IR) of subjects with locally confirmed BRAF V600E-mutation positive melanoma that has metastasized to the brain without symptoms and have not undergone prior local therapy for brain metastases (Cohort A).
    E.2.2Secondary objectives of the trial
    1. To assess cohort B for IR of subjects with locally confirmed BRAF V600E cutaneous melanoma with metastases to the brain confirmed by MRI, asymptomatic with prior local therapy for brain metastases; ECOG score of 0-1.
    2. To assess cohort C for IR of subjects with locally confirmed BRAF V600 D/K/R cutaneous melanoma with metastases to the brain confirmed by MRI, asymptomatic, with or without prior local therapy; ECOG score of 0-1.
    3. To assess cohort D for IR of subjects with locally confirmed BRAF V600 D/E/K/R cutaneous melanoma with metastases to the brain confirmed by MRI, symptomatic; with or without prior local therapy; ECOG score of 0-2.
    4. To assess Cohorts A, B, C and D for Disease Control for intracranial, extracranial and overall response (IDC, EDC and ODC respectively)
    5. To assess Cohorts A, B, C and D for extracranial response rate (ER)
    6. To assess Cohorts A, B, C and D for overall response rate (OR) For further information please view protocol section 2 page 30
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Is ≥ 18 years of age
    2. Has signed written informed consent.
    3. ECOG score of 0-1 for Cohorts A, B and C and ECOG score of 0-2 for Cohort D.
    4. Histologically confirmed via CLIA-certified assay for cutaneous metastatic melanoma (Stage IV; See Appendix 1 for staging), and determined to be V600 E, K, D or R. BRAF V600E mutation status for the subjects in Cohort A will be determined prospectively by the THxIDTM BRAF assay conducted in a central reference laboratory. Subjects in ALL cohorts are eligible to enroll based on local test results. Certified local test results will be subjected to retrospective central confirmation by a GSK designated assay.
    5. May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma including chemo-, cytokine-, immune-, biological- and vaccine therapy. Prior temozolomide for brain metastases and adjuvant interferon are acceptable and does not count toward the two previous systemic treatment regimens.
    6. Must be able to undergo MRI and have at least one measurable intracranial lesion for which all of the following criteria have to be met:
    a. Previously untreated or progressive according to RECIST 1.1 (>/= 20% increase in longest diameter on baseline scan) after previous local therapy
    b. Largest diameter of >/= 0.5cm diameter but </= 4cm as determined by contrast-enhanced MRI.
    c For target lesions with diameter of > 0.5cm but </= 1 cm documented measurement by a neuroradiologist/appropriately qualified radiologist /neurosurgeon is required.
    d For all lesions with a diameter of >/= 3cm but </= 4 cm documented measurement by a neuroradiologist / appropriately qualified radiologist /neurosurgeon is required.
    7. All prior anti-cancer treatment related toxicities (except alopecia) must be <= Grade 1 according to Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0; National Cancer Institute (NCI 2009) at the time of entry a.http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
    8. Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
    9. Must have adequate organ function as defined in Table 2 please view the protocol.
    10. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment and agree to use effective contraception, from 14 days prior to enrollment, throughout the treatment period, and for 4 months after the last dose of study treatment.
    11. Subjects registered in France: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
    E.4Principal exclusion criteria
    1. Neurological symptoms related to brain metastasis except for Cohort D where subjects can be symptomatic.
    2. Prior treatment with a BRAF inhibitor or a MEK inhibitor.
    3. Known ocular or primary mucosal melanoma
    4. Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, within the last 3 weeks, or chemotherapy without delayed toxicity within the last 2 weeks preceding the first dose of the combination. Prior systemic treatment in the adjuvant setting is allowed (same timelines as above). (Note: Ipilimumab treatment must end at least 8 weeks prior to enrollment.)
    5. Treatment with stereotactic radiosurgery within 14 days prior to start of study treatment, or treatment with whole-brain radiation within 28 days prior to study treatment.
    6. Any presence of leptomeningeal disease or any parenchymal brain metastasis >4.0 cm in diameter.
    7. Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is longer, prior to dosing.
    8. Current or expected use of a prohibited medication
    9. History of malignancy with confirmed activating RAS mutation at any time. Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
    10. History of malignancy other than disease under study within 3 years, of study enrolment with exceptions below. Exception: Subjects with a history of completely resected non-melanoma skin cancer, or subjects with indolent second malignancies are eligible.
    11. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the investigator, could interfere with the subject’s safety, obtaining informed consent, or compliance with study procedures.
    12. A history of Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and/or HCV will be permitted).
    13. A history or evidence of cardiovascular risk including any of t3e following:
    a. Current LVEF <LLN
    b. A QT interval corrected for heart rate using the Bazett’s formula (QTcB; ≥480 msec; See Appendix 4
    c. A history or evidence of current clinically significant uncontrolled arrhythmias;
    Clarification: Subjects with atrial fibrillation controlled for >30 days prior to dosing are eligible.
    d. A history (within 6 months prior dosing) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty,
    e. A history or evidence of current ≥Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines.
    f. Treatment refractory hypertension defined as a blood pressure of systolic >140mmHg and/ or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy;
    g. Patients with intra-cardiac defibrillators.
    h. Abnormal cardiac valve morphology (≥grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
    14. A history or current evidence of retinal vein occlusion (RVO)
    15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/ or dimethyl sulfoxide (DMSO).
    16. Pregnant or nursing females.
    17. History of Interstitial lung disease or pneumonitis
    18. Subjects registered in France and Germany: French/German Subjects please refer to Appendix 9 for country specific guidance.
    E.5 End points
    E.5.1Primary end point(s)
    • IR is defined as the proportion of subjects with a confirmed intracranial complete response (CR) or partial response (PR) as per investigator assessment using modified RECIST 1.1 guidelines [Eisenhauer, 2009].
    E.5.1.1Timepoint(s) of evaluation of this end point
    Intracranial will be assessed at baseline, Week 4, Week 8, and every 8 weeks thereafter. After Week 40, disease assessments may be performed every 12 weeks
    E.5.2Secondary end point(s)
    • IR is defined as the percentage of subjects with a confirmed intracranial complete response (CR) or partial response (PR) as per investigator assessment using modified RECIST 1.1 guidelines [Eisenhauer, 2009].
    • Intracranial Disease Control (IDC) is defined as CR+PR+SD for intracranial, extracranial, and overall disease control
    • Extracranial response (ER), defined as the percentage of subjects with a best extracranial response of a confirmed CR or PR by investigator assessment using modified RECIST 1.1
    • Overall response (OR), defined as the percentage of subjects with a best overall confirmed response of CR or PR by investigator assessment.
    • Duration of intracranial, extracranial and overall response (DIR, DER and DOR), defined as the time from first documented evidence of CR or PR until time of first documented intracranial, extracranial and overall disease progression.
    • PFS, defined as the interval between first dose and the earliest date of disease progression or death due to any cause
    • Overall survival (OS), defined as the time from first dose until death due to any cause.
    • Assessment of safety of dabrafenib and trametinib measured by the frequency and severity of adverse events, skin assessments, laboratory abnormalities, vital signs, and assessment data (12-lead electrocardiograms (ECG), echocardiograms, and clinical monitoring/observation including neurological examination).
    Exploratory endpoints:
    • Tumour DNA, RNA, and protein content, other tumour tissue aberrations, clinical outcome and their association of the mutation profile with tumour response.
    • BRAF and other cancer gene mutations in cfDNA, cfDNA burden and their association with tumour response
    • Germline genetic variants and their association with safety measures (as listed under secondary endpoints), , and with tumour response.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Intracranial and extracranial disease will be assessed at baseline, Week 4, Week 8, and every 8 weeks thereafter. After Week 40, disease assessments may be performed every 12 weeks.
    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 No
    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 Yes
    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.8.2.4Number 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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA26
    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
    France
    Germany
    Italy
    Spain
    United States
    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 study will be completed when either all subjects are dead or lost to follow-up, or all subjects still in follow-up have had at least 3 years follow-up from the date of first dose of study treatment, whichever is earlier.
    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: 96
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 24
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 80
    F.4.2.2In the whole clinical trial 120
    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)
    Subjects who discontinue treatments will have safety assessments at discontinuation and during follow-up and will be followed for survival and new anti-cancer therapy . Subjects who discontinue treatment without progression will be followed for progression (Table 19). Survival and new anti-cancer therapy follow-up will continue until either all subjects are dead, withdrawn consent or lost to follow-up, or all subjects still in follow-up have had at least 3 years follow-up.
    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 Decision2014-05-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-02-27
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-02-14
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
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