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    The EU Clinical Trials Register currently displays   43843   clinical trials with a EudraCT protocol, of which   7282   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:2012-004537-16
    Sponsor's Protocol Code Number:MO11/10085
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2012-12-11
    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 ConcernedUK - MHRA
    A.2EudraCT number2012-004537-16
    A.3Full title of the trial
    An Open Label Multi-Centre Preoperative Window of Opportunity Study of Afatinib in Stage Ia to IIb Non-Small Cell Lung Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    ABLE Trial – Afatinib Before Lung surgEry
    A.3.2Name or abbreviated title of the trial where available
    ABLE Trial – Afatinib Before Lung surgEry
    A.4.1Sponsor's protocol code numberMO11/10085
    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 SponsorUniversity of Leeds
    B.1.3.4Country
    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 supportBoehringer Ingleheim Ltd.
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity of Leeds
    B.5.2Functional name of contact pointDr Clive Mulatero
    B.5.3 Address:
    B.5.3.1Street AddressLevel 4 Bexley Wing, St James's University Hospital
    B.5.3.2Town/ cityLeeds
    B.5.3.3Post codeLS9 7TF
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01132068650
    B.5.5Fax number01130268320
    B.5.6E-mailclive.mulatero@leedsth.nhs.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 nameAfatinib(Tomtovok)
    D.3.2Product code BIBW 2992
    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 INNN-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide
    D.3.9.1CAS number 439081-18-2
    D.3.9.3Other descriptive nameAfatinib (BIBW2992)
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-small cell lung cancer
    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 LLT
    E.1.2Classification code 10025051
    E.1.2Term Lung cancer non-small cell stage II
    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
    The principal research question is whether a reduction in the amount of energy the cancer uses can be seen when a short course of afatinib is given to early stage lung cancer patients before surgery?
    E.2.2Secondary objectives of the trial
    Secondary objectives

    1. To see if a reduction in tumour volume can be measured by CT imaging after the patients have been taking afatinib for fifteen days.

    2. To assess the safety and tolerability of giving afatinib before lung surgery.

    Exploratory Objectives

    1. To look for genetic mutations (not inherited but acquired since birth) that could be causing cancers to grow, such as those for EGFR and ALK genes.

    2. To determine how much afatinib gets in to cancer tissue when given as a tablet.

    3. To measure the effect inside cancer cells in response to afatinib by looking at changes to signal proteins inside cells when afatinib is taken.

    4. To see if it will be feasible to offer tailored adjuvant targeted therapies such as afatinib to NSCLC patients in a larger Phase III clinical trial.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able to give written informed consent and willing to follow the study protocol.
    2. Age ≥ 18 years.
    3. Histologically confirmed resectable non-small cell lung cancer, meeting one of the following clinical staging criteria:
    a. Stage 1A or 1B (T1-2, N0).
    b. Stage II (T1-2, N1 or T3, N0).

    The number of participants with predominatly squamous histology eligible to enter the study will be capped at twenty.

    4. Measurable disease by contrast-enhanced CT scan:
    a. The primary tumour must have a diameter on CT imaging of at least 8mm.
    b. The primary tumour must have an SUVmax on FDG-PET of at least 3.0.
    5. ECOG PS 0 – 1.
    6. Eligible for complete surgical resection, defined as the appropriate pulmonary parenchymal resection including lobectomy, bi-lobectomy, sleeve lobectomy, or pneumonectomy.
    7. Adequate baseline haematopoietic, hepatic and renal function, defined as follows:
    a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
    b. Platelet count ≥100 x 109/L.
    c. Bilirubin ≤ 1.5 x ULN.
    d. ALT or AST ≤ 3 x ULN.
    e. Creatinine ≤ 1.5 x ULN.
    8. Ability to take and absorb oral medications.
    9. Female patients of childbearing potential (i.e. pre-menopausal females, females who have been menopausal for < 1 year and not surgically sterilized, or males not surgically sterilized) must provide a negative pregnancy test (urine or serum) ≤ 7 days before study treatment begins and must agree to practice effective contraceptive measures for the duration of study drug therapy and for at least 30 days after completion of study drug therapy.
    10. Male participants must agree to use a barrier method of contraception for the duration of the study if sexually active with a female of childbearing potential and must continue to do so for 30 days after the end of treatment.
    E.4Principal exclusion criteria
    1. Tumours of mixed histology (combined small cell and non-small cell carcinoma), pulmonary carcinoid tumours, or large cell carcinoma with evidence of neuroendocrine features. However non-small cell tumours with mixed adenocarcinoma and squamous cell carcinoma histology are eligible.
    2. Patients with preoperative radiological evidence of N2 disease by either PET/CT or CT scan (i.e. radiological evidence of metastasis to ipsilateral mediastinal and subcarinal lymph nodes) that is confirmed as N2 disease histologically/cytologically.
    3. Any prior or concurrent systemic chemotherapy for NSCLC.
    4. Any prior or concurrent radiotherapy for NSCLC.
    5. Any prior treatment with any EGFR inhibitor.
    6. Current treatment with potent P-glycoprotein inhibitors or inducers.
    7. Any other concurrent malignancy with the exception of non-melanoma skin cancers.
    8. Known pre-existing interstitial lung disease.
    9. Significant or recent (within 6 months) acute gastrointestinal disorders with diarrhoea as a major symptom e.g. Crohn’s disease, malabsorption or CTC grade ≥ 2 diarrhoea of any aetiology.
    10. History or presence of clinically relevant cardiovascular abnormalities such as:
    d. Uncontrolled hypertension.
    e. Congestive heart disease NYHA Classification Grade 3.
    f. Unstable angina or poorly controlled arrhythmia.
    11. Congestive Cardiac failure, with left ventricular ejection fraction of < 50% as measured by echocardiography/Gated SPECT/MUGA imaging.
    12. Uncontrolled infection, or any serious illness or organ system dysfunction which in the opinion of the investigator would either compromise participant safety or interfere with the evaluation of the safety of the test drug.
    13. Pregnant (positive pregnancy test) or breast feeding women.
    14. History of a poorly controlled neurologic or psychiatric condition that, in the Investigator’s opinion, is likely to interfere with the participant’s ability to participate and / or to comply with the requirements of the study.
    15. Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
    16. Ocular inflammatory or chronic infectious conditions.
    17. Poorly controlled diabetes mellitus.
    18. Known or suspected active drug or alcohol abuse.
    19. Participation in another investigational drug trial whilst on-study.
    20. Known hypersensitivity to afatinib or to any of the excipients contained in the tablet preparation.
    Superior vena cava syndrome.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will assess whether a mean reduction in SUVmax of 10% can be observed in the patient group enrolled in the study by 18F-FDG PET imaging after they have received fifteen days (+2 if necessary)of therapy with oral afatinib.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The individual PET/CT images will be analysed on an ongoing basis during the study, This will be overseen by the 'Core Laboratory'. The final evaluation of the primary endpoint will be preformed following completion of participation in the study of 59 evaluable patients. This evaluation is expected to take approximately six months.
    E.5.2Secondary end point(s)
    1. To determine the reduction in tumour size on day fifteen 18F-PET/CT imaging assessed by volumetric CT measurement.

    2. To assess safety and tolerability of preoperative afatinib.

    3. To assess the feasibility of offering tailored adjuvant targeted therapies to NSCLC patients in Phase III clinical trial context.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. It is anticipated that analysis of volumetric CT assessments will be completed within six months of completion of the study.

    2. Formal safety and tolerability reviews will be preformed after 10 and 30 consecutive patients have been recruited to the study. Further reviews will take place as necessary at the request of the Data Monitoring and Ethics Committee who will meet at six monthly intervals. A final toxicity and tolerability analysis will be preformed upon completion of the study.

    3. The feasibility of performing a Phase III trial in this context will be assessed upon completion of the study.
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned3
    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 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
    Upon completion of the last participant’s four-week postoperative follow-up visit.
    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 months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    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: 34
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 35
    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 state69
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 69
    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)
    Afatinib will not be available to participants directly following the end of study as it remains an unlicensed investigational product. Patients will be informed of this during the informed consent process.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation N/A - none used
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-01-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-01-08
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2016-08-01
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