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    Summary
    EudraCT Number:2011-003608-19
    Sponsor's Protocol Code Number:UCL/09/0426
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-11-01
    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 number2011-003608-19
    A.3Full title of the trial
    Trial of afatinib (BIBW 2992) in suspected or confirmed mutant EGFR lung cancer patients unfit for chemotherapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A trial which will look into the effects of giving a drug to patients with non small cell lung cancer with the aim of improving survival outcomes.
    A.3.2Name or abbreviated title of the trial where available
    TIMELY
    A.4.1Sponsor's protocol code numberUCL/09/0426
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01415011
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity College London
    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 supportBoehringer Ingelheim Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity College London
    B.5.2Functional name of contact pointLaura Hughes
    B.5.3 Address:
    B.5.3.1Street AddressCancer Research UK & UCL Cancer Trials Centre
    B.5.3.2Town/ city90 Tottenham Court Road
    B.5.3.3Post codeW1T 4TJ
    B.5.4Telephone number02076799284
    B.5.5Fax number02076799871
    B.5.6E-mailctc.timely@ucl.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 nameafatinib (BIBW 2992)
    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 INNAfatinib
    D.3.9.2Current sponsor codeBIBW 2992
    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 number40 to 30 or 20
    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 Giotrif
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim International GmbH
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameGiotrif
    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 INNAfatinib
    D.3.9.3Other descriptive nameGiotrif
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30 to 20
    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) 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
    Cancer of the lung
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10025064
    E.1.2Term Lung carcinoma
    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 examine the efficacy and safety of afatinib (BIBW 2992) in patients with non-small cell lung cancer and suspected or confirmed EGFR mutation considered unfit for chemotherapy. Primary outcome measure is progression free survival at 6 months.
    E.2.2Secondary objectives of the trial
    The secondary objectives for this trial are:
    • Overall response
    • Overall survival
    • Change in patients' performance status at 1 month
    • Safety
    • Progression free survival in patients aged 70 and over
    • Treatment compliance
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    TIMELY Translational Study

    Baseline: Collection of EDTA blood (germ-line pharmacogenomics), serum (epigenetic studies), plasma and urine for exploratory proteomic and metabonomic studies. Surplus somatic DNA and archival paraffin embedded formalin fixed diagnostic tissue will be collected if available.

    On treatment: Collection of serum, plasma, and urine at intervals of 3 cycles until progression.

    On progression: Final collection of serum, plasma, and urine. In addition, patients progressing will be asked to provide a biopsy of a progressive site (optional).
    E.3Principal inclusion criteria
    Patient Inclusion Criteria

    1. Any stage not suitable for radical treatment
    2.Either:
    Confirmed activating EGFR mutation (exons 18-21; eg L858R, exon 19 deletions, exon 20 insertions, T790M, this list is not exhaustive) and WHO PS 0-3

    Or
    •No tissue suitable for EGFR genotyping, failed genotype, or EGFR genotyping unavailable, and
    •NSCLC Adenocarcinoma sub-type (including any WHO variant – see Appendix 4), and
    •Eligible smoking history:
    - Never smoker (<100 cigarettes in lifetime), or
    - Former smoker (stopped >1year ago and ≤10 pack-years)
    •and WHO PS 0-2
    3. Predicted life expectancy ≥ 8 weeks
    4. Unsuitable for or patient declining chemotherapy due to significant co-morbidity
    5. Measurable disease according to RECIST version 1.1
    6. Age 18 or over (no upper age limit)
    7. Adequate haematopoietic, hepatic and renal function defined as follows:
    • Absolute neutrophil count (ANC) ≥1.5 x 109/L and platelet count ≥100 x 109/L
    • Bilirubin ≤1.5 x ULN, ALT/AST(SGPT/SGOT) ≤3 x ULN (or ≤ 5 x ULN in cases of liver metastases)
    8.Serum creatinine clearance ≥45 ml/min using any local method
    9. Palliative radiotherapy allowed unless to a solitary target lesion
    10. Written informed consent
    E.4Principal exclusion criteria
    Exclusion Criteria

    1. Previous treatment with BIBW 2992, or any EGFR-directed inhibitor
    2. Any concurrent anticancer systemic therapy
    3. Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and registration
    4. Suitable for radical radiotherapy
    5. Palliative radiotherapy within 2 weeks prior to registration
    6. Palliative radiotherapy to a solitary target lesion
    7. Surgery (other than biopsy) within 4 weeks prior to registration
    8. Inability to take oral medication, requirement for intravenous feeding, active peptic ulcer, prior surgical procedures affecting absorption or, any medical co-morbidity affecting gastrointestinal absorption
    9. Patients with current or pre-existing interstitial lung disease
    10. Active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient’s participation in the trial
    11. Significant or recent acute gastrointestinal abnormalities with diarrhoea as a major symptom e.g., Crohn’s disease, mal-absorption, or CTCAE v4.0 Grade ≥3 diarrhoea of any etiology at baseline
    12. Active brain metastases (defined as stable for <4 weeks and/or symptomatic and/or requiring treatment with anticonvulsants and/or leptomeningeal disease. Steroids will be allowed if administered as a stable (same) dose for at least one month before trial entry
    13. Any other current malignancy or malignancy diagnosed within the past five years (other than non-melanomatous skin cancer and in situ cervical cancer)
    14. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3 or more, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to registration
    15. Symptomatic left ventricular failure with NYHA classification of 3 or more
    16. Active viral hepatitis and/or known HIV positive
    17. Known or suspected active drug or alcohol abuse
    18. Use of any investigational drug within 8 weeks of registration
    19. Known allergy to BIBW 2992 or other ingredients
    20. Patients who have not been on the same dose of steroids for at least 4 weeks.
    21. Inability to understand or to comply with the requirements of the trial, trial protocol or to provide informed consent
    22. Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial
    23. Women who are pregnant or breast feeding
    24. Requirement for treatment with any of the prohibited concomitant medications listed in protocol
    E.5 End points
    E.5.1Primary end point(s)
    Progression free survival rate at 6 months.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Progression-free survival at 6 months will be calculated as the time between the date of registration and date of first progression or death (from any cause), whichever occurs first. This will be performed for all patients, and then separately for those with known or unknown EGFR mutations.
    E.5.2Secondary end point(s)
    • Overall response
    • Overall survival
    • Change in performance status at 1 month
    • Safety
    • Progression free survival in patients aged 70 and over
    • Treatment compliance
    E.5.2.1Timepoint(s) of evaluation of this end point
    Overall Response:
    Assessed by CT scan of chest & abdomen 4 weeks after registration, then every 8 calender weeks until disease progression. CT scans every 12 weeks if patient is still on afatinib (BIBW 2992) after 1 year of treatment.

    Overall Survival:
    This will be measured in days, from the first day of treatment to the day of death.

    Change in performance status at 1 month:
    Change will be measured at 1 month.

    Safety:
    Safety will be assessed at each patient visit i.e. baseline, fortnightly for the first 2 cycles, monthly for 12 months and 2 monthly thereafter.

    Progression free survival in patients aged 70 and over:
    At progression or patient death.

    Treatment Compliance:
    Compliance will be examined based on the time between starting treatment and stopping it completely.
    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 concerned30
    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
    For regulatory purposes the end of the trial will be 3 months after the last patient on trial discontinues afatinib (BIBW 2992), or 2 months after the final trial analysis and report is available (whichever occurs first) at which point the ‘declaration of end of trial’ form will be submitted to participating regulatory authorities and ethical committees, as required.
    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 months2
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months2
    E.8.9.2In all countries concerned by the trial days1
    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: 0
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 0
    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 state37
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 37
    F.4.2.2In the whole clinical trial 37
    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)
    Each patient will take the study drug while on the trial for the period specified by the protocol i.e. until disease progression, toxicity or patient/clinician decision to stop. Patients who are still taking the study drug following the declaration of end of trial and deriving benefit will continue to be supplied the study drug until disease progression, toxicity or clinician/patient decision to stop.
    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 Decision2011-12-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-12-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-11-30
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