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    Summary
    EudraCT Number:2011-001161-41
    Sponsor's Protocol Code Number:BRF113928
    National Competent Authority:Norway - NOMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-10-17
    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 ConcernedNorway - NOMA
    A.2EudraCT number2011-001161-41
    A.3Full title of the trial
    A Phase II study of the selective BRAF kinase inhibitor
    GSK2118436 in subjects with advanced non-small cell lung
    cancer and BRAF mutations
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to test a new drug for treating non-small cell lung cancer
    A.4.1Sponsor's protocol code numberBRF113928
    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 SponsorGlaxoSmithKline Research and Development Limited
    B.1.3.4CountryUnited Kingdom
    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 supportGlaxoSmithKline
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline
    B.5.2Functional name of contact pointClinical Trials Helpdesk
    B.5.3 Address:
    B.5.3.1Street AddressIron Bridge Road, Stockley Park West
    B.5.3.2Town/ cityUxbridge, Middlesex
    B.5.3.3Post codeUB11 1BU
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number442089904466
    B.5.5Fax number442089901234
    B.5.6E-mailGSKClinicalSupportHD@gsk.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 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.3.9.2Current sponsor codeGSK2118436
    D.3.9.3Other descriptive nameN-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzene sulfonamide, methanesulfonate salt
    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 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.3.9.2Current sponsor codeGSK2118436
    D.3.9.3Other descriptive nameN-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-luorophenyl}-2,6-difluorobenzene sulfonamide, methanesulfonate salt
    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.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
    Advanced non-small cell lung cancer and BRAF mutations
    E.1.1.1Medical condition in easily understood language
    Lung cancer
    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 PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung 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 overall response rate (ORR) in subjects with stage IV or relapsed BRAF V600E mutant non-small cell lung cancer administered GSK2118436 as a single agent.
    E.2.2Secondary objectives of the trial
    • To assess progression free survival (PFS), duration of response and overall survival (OS) in subjects with stage IV or relapsed BRAF V600E mutant non-small cell lung cancer administered GSK2118436 as a single agent.
    • To further characterize the safety and tolerability of GSK2118436 when administered as a single agent to subjects with stage IV or relapsed BRAF V600E mutant non-small cell lung cancer.
    • To characterize the population pharmacokinetics of GSK2118436
    and identify important determinants of variability.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects eligible for enrolment in the study must meet all of the following criteria:
    1. Signed written informed consent;
    2. Histologically- or cytologically-confirmed diagnosis of NSCLC Stage IV (according to AJCC Staging 7th Edition);
    3. Documented tumor progression (based on radiological imaging) after receiving at least one prior approved platinum-based chemotherapy regimen for advanced stage/metastatic NSCLC;
    Note: Additional lines of treatment including maintenance therapy with singleagents or combination regimens including investigational anti-cancer drugs are allowed
    4. Measurable disease according to RECIST 1.1
    5. Male or female ≥18 years of age;
    6. Anticipated life expectancy of at least 3 months;
    7. Presence of a V600E BRAF mutation in lung cancer tissue confirmed in a CLIA certified laboratory (or equivalent) (see Section 7.1.1 of study protocol for testing details, as well as additional requirements regarding central confirmation);
    8. Able to swallow and retain oral medication;
    9. Women with child-bearing potential must be willing to practice acceptable methods
    of birth control during the study (See Section 7.4of study protocol);
    NOTE: Oral contraceptives are not reliable due to potential drug-drug interaction with GSK2118436
    10. Women of childbearing potential must have a menstrual history inconsistent with pregnancy and a negative serum pregnancy test within 14 days before the first dose of study medication and agree to use effective contraception, as defined in
    Section 7.4 of the study protocol, during the study;
    11. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;
    12. Must have adequate organ function as defined by the following baseline values:
    • Absolute neutrophil count (ANC) ≥1.5x109/L
    • Hemoglobin ≥9 g/dL
    • Platelets ≥100x109/L
    • Serum bilirubin ≤1.5 x upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN
    • Serum creatinine ≤1.5 mg/dL (if serum creatinine is >1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and Gault; creatinine clearance must be > 50 mL/min);
    • Prothrombin time /International normalized ratio (INR) and partial
    thromboplastin time ≤1.3xULN
    • Left ventricular ejection fraction ≥ institutional lower limit of normal
    13. French subjects: 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
    Subjects meeting any of the following criteria must not be enrolled in the study:
    1. Previous treatment with a BRAF or MEK inhibitor;
    2. Anti-Cancer therapy including chemotherapy, radiation-therapy, immunotherapy, biologic therapy or major surgery within 14 days prior to start of study therapy;
    3. Use of any investigational anti-cancer drug within 14 days or 5-half-lives prior to start of study therapy;
    4. Current use of a prohibited medication or expected to require any of these medications during treatment with GSK2118436 (See Section 6.2 of study protocol);
    5. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) Grade 2 or higher from previous anti-cancer therapy, except alopecia;
    6. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the GSK medical
    monitor for guidance to enrol the subject;
    7. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. Subjects with laboratory evidence of HBV clearance may be enrolled;
    8. A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency;
    9. History of another malignancy;
    Exception: (a) Subjects who have been successfully treated and are disease-free for 3 years, (b) a history of completely resected non-melanoma skin cancer, (c) successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent prostate cancer (definition: clinical stage T1 or T2a, Gleason score ≤ 6, and PSA < 10 ng/mL) requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from lung cancer target and nontarget
    lesions are eligible
    10. Subjects with brain metastases are excluded if their brain metastases are:
    • Symptomatic OR
    • Treated (surgery, radiation therapy) but not clinically and radiographically stable 3 weeks after local therapy(as assessed by contrast enhanced MRI), OR
    • Asymptomatic and untreated but > 1 cm in the longest dimension
    11. The following cardiac abnormalities:
    • Corrected QT (QTc) interval ≥480 msecs
    • History of acute coronary syndromes (including unstable angina) within the past 24 weeks
    • Coronary angioplasty, or stenting within the past 24 weeks
    • Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
    • Abnormal cardiac valve morphology (≥ Grade 2) documented by
    echocardiogram (subjects with Grade 1 abnormalities [ie, mild
    regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study
    • History of known arrhythmias (except sinus arrhythmia) within the past 24 weeks
    12. Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension, etc), 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;
    13. Pregnant, lactating or actively breastfeeding females.
    E.5 End points
    E.5.1Primary end point(s)
    ORR, which is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) by investigator assessment as per RECIST 1.1 criteria
    E.5.1.1Timepoint(s) of evaluation of this end point
    Scans are every 6 weeks from Week 1-36, then every 12 weeks after Week 36.
    E.5.2Secondary end point(s)
    • PFS defined as the interval between first dose and the earliest date of disease progression or death due to any cause
    • Duration of response, defined for the subset of subjects with confirmed CR or PR, as the time from first documented evidence of CR or PR until time of first documented disease progression or death due to any cause
    • OS defined as the time from first dose until death due to any cause
    • Measurements used to evaluate safety will include physical and dermatological examinations, vital signs, 12-lead ECGs, ECHO, clinical laboratory tests, and AEs
    • GSK2118436 population PK parameters such as apparent clearance (CL/F) and volume of distribution (V/F), and relevant covariates which may influence exposure (e.g. age, weight, or disease related covariates)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Scans are every 6 weeks from Week 1-36, then every 12 weeks after Week 36.
    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 Yes
    E.6.7Pharmacodynamic Yes
    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.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    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
    Korea, Republic of
    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 considered complete when a minimum of 70% of subjects have died or five years have passed since the last subject was entered on the study, whichever comes first. Subjects who are still benefiting from GSK2118436 at the time of study completion may have the option to enter the rollover study, Protocol BRF114144, an open-label, rollover study of GSK2118436.
    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 months8
    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: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 20
    F.4.2.2In the whole clinical trial 40
    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)
    All subjects who permanently discontinue study medication will be followed for survival and new anti-cancer therapy until study completion. Subjects who are still benefiting from GSK2118436 at the time of study completion may have the option to enter the rollover study, Protocol BRF114144, an open-label, rollover study of GSK2118436.
    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 Decision2013-01-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-12-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-01-07
    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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