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   43865   clinical trials with a EudraCT protocol, of which   7286   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:2015-002269-47
    Sponsor's Protocol Code Number:STH18441
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2015-09-28
    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 ConcernedUK - MHRA
    A.2EudraCT number2015-002269-47
    A.3Full title of the trial
    Investigating the potential clinical benefit of Selumetinib in resensitising advanced iodine refractory differentiated thyroid cancer to radioiodine therapy.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Investigating the potential clinical benefit of Selumetinib in re-sensitising advanced iodine refractory differentiated thyroid cancer to radioiodine therapy.
    A.3.2Name or abbreviated title of the trial where available
    SEL-I-METRY
    A.4.1Sponsor's protocol code numberSTH18441
    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 SponsorSheffield Teaching Hospitals NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    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 supportCancer Research UK
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationLeeds Institute of Clinical Trials Research
    B.5.2Functional name of contact pointLICTR
    B.5.3 Address:
    B.5.3.1Street Address71-75 Clarendon Road
    B.5.3.2Town/ cityLeeds
    B.5.3.3Post codeLS2 9PH
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number0113 343 9141
    B.5.6E-mailS.Flynn@leeds.ac.uk
    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 nameSelumetinib
    D.3.2Product code AZD6244
    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 INNSelumetinib
    D.3.9.1CAS number 606143-52-6
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Iodine-refractory thyroid cancer of papillary, follicular, Hürthle cell or poorly differentiated carcinoma
    E.1.1.1Medical condition in easily understood language
    Iodine refractory thyroid cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10071029
    E.1.2Term Thyroid cancer stage III
    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 18.0
    E.1.2Level PT
    E.1.2Classification code 10016935
    E.1.2Term Follicular thyroid 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 18.0
    E.1.2Level PT
    E.1.2Classification code 10071030
    E.1.2Term Thyroid cancer stage IV
    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 18.0
    E.1.2Level PT
    E.1.2Classification code 10066474
    E.1.2Term Thyroid 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 18.0
    E.1.2Level PT
    E.1.2Classification code 10055107
    E.1.2Term Thyroid cancer metastatic
    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 18.0
    E.1.2Level PT
    E.1.2Classification code 10033701
    E.1.2Term Papillary thyroid 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 efficacy of Selumetinib followed by radioiodine therapy in iodine refractory patients with differentiated thyroid cancer demonstrating increased iodine uptake following initial treatment with Selumetinib.

    The principal objective is to determine whether this schedule may lead to increased progression-free survival compared to historical control data.
    E.2.2Secondary objectives of the trial
    To assess the safety and toxicity of Selumetinib

    To assess efficacy based on response and overall survival to Selumetinib followed by radioiodine therapy

    To determine the rate of iodine uptake in metastatic lesions in iodine refractory patients with differentiated thyroid cancer treated with Selumetinib.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Diagnosed with locally advanced or metastatic differentiated thyroid cancer (papillary, follicular, Hürthle cell, or poorly differentiated carcinoma) with at least one measurable lesion as measured by computed tomography (CT) or magnetic resonance imaging (MRI)
    • Participants must have iodine refractory disease, defined below:
    One or more measurable lesions that do not demonstrate iodine uptake on a previous radioiodine scan (diagnostic uptake or post therapy)
    OR
    One or more measurable lesions that have progressed by RECIST 1.1 criteria within 12 months of I-131 therapy, despite demonstrable radioiodine avidity at the time of that treatment
    • Participants must have radiological progression by RECIST 1.1 criteria within the prior 12 months
    • Measurable disease by RECIST 1.1 criteria.
    • ECOG Performance Status ≤ 1 and able to tolerate radioiodine therapy
    • Life expectancy of at least 12 weeks
    • Required laboratory values within 14 days of day 1 of treatment:
    o Adequate thyroid-stimulating hormone (TSH) suppression < 0.5 mU/L
    o Creatinine clearance >50 ml/min,
    o Absolute Neutrophil Count ≥1.5x109/L (1500 per mm3)
    o Platelets ≥100x109/L (100,000 per mm3)
    o Haemoglobin >9.0 g/dL
    o Serum bilirubin ≤1.5 x upper limit of normal (ULN)
    o Patients with no liver metastasis must have AST or ALT ≤ 2.5 x ULN
    o Patients with liver metastasis must have AST or ALT ≤ 5 x ULN. If patients have AST or ALT > 3.5 x ULN and ≤ 5 x ULN they must have an ALP≤ 6 x ULN
    Patient’s with Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology) will be eligible.
    • Able to give informed consent and willing to follow trial protocol.
    • Aged over 18
    • Female participants of child-bearing potential must have a negative pregnancy test within 24 hours prior to starting therapy and agree to use dual methods of contraception for the duration of the trial and 6 months after completing treatment. Male participants must agree to use a barrier method of contraception for the duration of the trial and 4 months after completing treatment, if sexually active with a female of child-bearing potential.
    E.4Principal exclusion criteria
    • Foci of anaplastic thyroid cancer identified on histology
    • Able to receive curative surgery or radiation therapy
    • Major surgery with the exception of surgical placement for vascular access, open biopsy, or significant traumatic injury ≤ 30 days prior to registration
    • Previous or concurrent cancer distinct in primary site or histology from thyroid cancer within previous 5 years, except for cervical cancer in situ, treated basal cell carcinoma, squamous cell carcinoma of the skin or superficial bladder tumour
    • Have received or are receiving an IMP or other systemic anticancer treatment within 4 weeks prior to the first dose of study treatment (6 weeks for nitrosoureas, mitomycin, and suramin), or within a period during which the IMP or anticancer treatment has not been cleared from the body (e.g. a period of 5 ‘half-lives’), whichever is the most appropriate and as judged by the investigator
    • Any unresolved toxicity ≥CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia
    • Prior exposure to Tyrosine Kinase, MEK, RAS or RAF inhibitors
    • Known or suspected allergy to Selumentinib or hypersensitivity to Selumetinib or any excipient agents or history of allergic reactions attributed to compounds of similar chemical or biologic composition to Selumetinib
    • Known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and / or radiation, and has been stable without requiring corticosteroids nor anti-convulsant medications for at least 4 weeks prior to the first dose of study medication
    • Requiring medication with high iodine content (e.g. amiodarone)
    • Participants who have had a iIodine contrast enhanced CT scan in previous 2 months

    • Ophthalmological conditions as follows:
    o Intra-ocular pressure >21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)
    o Current or past history of retinal pigment epithelial detachment (REPD)/central serous retinopathy or retinal vein occlusion
    • Any of the following cardiac conditions
    o Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy)
    o Acute coronary syndrome within 6 months prior to starting treatment
    o Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)
    o Symptomatic heart failure (NYHA grade II-IV), prior or current cardiomyopathy, or severe valvular heart disease
    o Prior or current cardiomyopathy including but not limited to the following:
     Known hypertrophic cardiomyopathy
     Known arrhythmogenic right ventricular cardiomyopathy
    o Severe valvular heart disease
    o Left ventricular ejection fraction <55% measured by echocardiography
    o Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
    o QTcF >450ms or other factors that increase the risk of QT prolongation
    • Known to be infected with human immunodeficiency virus (HIV) or hepatitis B (HBV) or C (HCV) virus
    • Any evidence of severe or uncontrolled systemic disease(e.g. unstable or uncompensated respiratory, cardiac, hepatic, or renal disease),, active infection(including hepatitis B, hepatitis C, HIV), active bleeding diatheses or renal transplant
    • Pregnant or breastfeeding females
    • Male or female patients of reproductive potential who and, as judged by the investigator, are not employing an effective method of birth control
    • Have evidence of any other significant clinical disorder or laboratory finding that, as judged by the investigator, makes it undesirable for the patient to participate in the study.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint for this trial is progression free survival at 12 months in patients with iodine-refractory thyroid cancer.

    Progression-free survival is calculated from the date of registration to first documented evidence of disease progression or death. Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression-free.
    E.5.1.1Timepoint(s) of evaluation of this end point
    This primary outcome will be evaluated 12 months following inclusion into the study.
    E.5.2Secondary end point(s)
    The secondary endpoints of this study are:

    To assess the safety and toxicity of selumetinib - toxicity will be reported based on adverse reactions, as graded by CTCAE V4.0, and determined by routine clinical assessments at each centre. Safety will be reported based on the occurrence of SAEs, SARs and SUSARs.

    To assess the radiological response rate for patients receiving radioiodine therapy - this will be assessed via 3 monthly CT scans for the first 12 months, 6 monthly thereafter, and will be based on RECIST v1.1

    To assess the overall survival - calculated from the date of registration to death. Patients who are still alive at the time of analysis will be censored at the last date they were known to be alive.

    To assess the proportion of patients with sufficient iodine uptake to warrant radioiodine therapy.
    E.5.2.1Timepoint(s) of evaluation of this end point
    These endpoints will be assessed:
    To assess the safety and toxicity of selumetinib - ongoing assessment.
    To assess the radiological response rate for patients receiving radioiodine therapy - following radioiodine therapy if achieved, 3-monthly for first 12 months then 6-monthly.
    To assess the overall survival - ongoing assessment
    To assess the proportion of patients with sufficient iodine uptake to warrant radioiodine therapy - at the end of selumetinib therapy
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 concerned8
    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
    Last data collection point of the last subject.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    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 years4
    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.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    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: 30
    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 state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 60
    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)
    Patients will be followed up until disease progression or they no longer wish to take part in the trial. At the end of the research, any further treatment a patient may need will be decided by their treating clinician on an individual basis. This is stated in the patient information sheet. There is no provision to provide Selumetinib outside of the remit of the trial.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-11-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-12-02
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    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-Mon Apr 29 18:47:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA