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    Summary
    EudraCT Number:2011-003408-19
    Sponsor's Protocol Code Number:WX/80-003
    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:2012-01-05
    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 number2011-003408-19
    A.3Full title of the trial
    A Phase I/II, open-label, dose-escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of the MEK inhibitor WX-554 in patients with solid tumours
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase I/II study of WX-554 in solid tumours
    A.4.1Sponsor's protocol code numberWX/80-003
    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 SponsorWILEX AG
    B.1.3.4CountryGermany
    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 supportWILEX AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationWilex AG
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressGrillparzerstraße 10
    B.5.3.2Town/ cityMunich
    B.5.3.3Post code81675
    B.5.3.4CountryGermany
    B.5.4Telephone number0049(0)894131380
    B.5.5Fax number0049(0)8941313899
    B.5.6E-mailinfo@wilex.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 nameWX-554
    D.3.2Product code WX-554
    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 INNnot yet defined
    D.3.9.2Current sponsor codeWX-554.3
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number25 to 50
    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
    Patients with advanced, metastatic and/or progressive solid tumours for whom there is no effective standard therapy available.
    E.1.1.1Medical condition in easily understood language
    Advanced 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 10049280
    E.1.2Term Solid tumour
    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
    Part 1:
    To determine the Optimum Biological Dose and Maximum Tolerated Dose for WX-554 (or only MTD if toxicity occurs before full target inhibition) and the recommended dose/dose schedules for Part 2.

    Part 2:
    To further determine the safety and tolerability of chronic treatment with WX-554

    E.2.2Secondary objectives of the trial
    Part 1:
    To determine the safety and tolerability of WX-554
    To determine the PK of WX 554 after oral dosing
    To assess the clinical activity of WX-554

    Part 2:
    To further determine the PK of WX 554 after oral dosing
    To further determine the PD activity of WX 554 after oral intake of the OBD/MTD dose in plasma, PBMC, skin and tumour biopsies
    To further determine the clinical activity of WX-554
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. 18 years old or older.

    2. Part 1 Dose Escalation: Patients with advanced, metastatic and/or progressive solid tumours for whom there is no effective standard therapy available.

    Part 2 Dose Expansion: Patients with advanced, metastatic and/or progressive solid tumours for whom there is no effective standard therapy available. Efforts will be made to enrol patients with tumours for which the MEK pathway is considered to play a significant role e.g. melanoma, thyroid, NSCLC, colon or pancreatic cancer.

    3. Evaluable or measurable disease.

    4. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.

    5. Life expectancy of >3 months, in the opinion of the Investigator.

    6. Able to take oral medications.

    7. Able to provide written informed consent.

    8. Willing to provide consent for biomarker analysis of existing paraffin-embedded tumour samples.

    9. Laboratory parameters (obtained within the Screening period):

    • Absolute neutrophils count ≥1.5x10E9/L;
    • Platelets ≥100 x10E9/L;
    • Haemoglobin ≥9 g/dL;
    • Total bilirubin ≤1.5 x ULN;
    • AST/ALT ≤ 2.5 x ULN (if liver metastases are present, ≤5 x ULN);
    • AP ≤ 2.5 x ULN (if bone metastases are present, ≤5 x ULN;
    • Serum creatinine ≤1.5 x ULN or estimated GFR of >50 mL/min based on the Wright formula .

    10. Negative hCG test in women of childbearing potential (defined as women ≤50 years of age or history of amenorrhea for ≤12 months prior to study entry). Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control (e.g. barrier methods with spermicides, oral or parenteral contraceptives and/or intrauterine devices) during the entire duration of the study and for 1 month after final administration of WX-554, or the patient must be surgically sterile (with documentation in the patient’s medical records).

    11. If there is a history of treated brain metastases, these must have been clinically stable for ≥4 weeks prior to enrollment. Steroid treatment must also be a stable or reducing dose during this time period.
    E.4Principal exclusion criteria
    1. First WX-554 administration planned within 4 weeks of receiving an investigational anti-cancer drug.

    2. Received major surgery, radiotherapy, or immunotherapy within 4 weeks of Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control.

    3. Received chemotherapy regimens with delayed toxicity within four weeks (6 weeks for prior nitrosourea or mitomycin C) of Cycle 1, Day 1. Received chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within two weeks of Cycle 1, Day 1.

    4. Clinically significant, unresolved toxicity from previous anti-cancer therapy greater than Grade 1 (except alopecia), as determined by NCI CTCAE v4.03 criteria.

    5. Previously received a MEK inhibitor.

    6. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.

    7. Known medical history of retinal vein occlusion, intraocular pressure greater than 21 mm Hg or patient considered at risk of retinal vein thrombosis.

    8. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

    9. Condition that in the Investigator's opinion would jeopardize compliance with the protocol.

    10. Known HIV positivity or active hepatitis B or C infection.

    11. History of clinically significant cardiac condition, including ischaemic cardiac event or myocardial infarction within 6 months, or unstable cardiac disease within 3 months of Cycle 1, Day 1.

    12. History of significant chronic or (re)current infection or intercurrent illness that could jeopardise patient safety, interfere with the objectives of the protocol or limit patient compliance with the study procedures, as determined by the Investigator.

    13. Pregnant or lactating female.
    E.5 End points
    E.5.1Primary end point(s)
    Part 1
    Primary:
    DLT evaluation in 3-6 patients at the end of 1 treatment cycle.
    PD assessment of ERK phosphorylation (pERK) in PBMC, skin and tumour biopsies, and assessment of TNF-alpha in plasma.

    Part 2
    Primary:
    On-going evaluation of AEs during treatment and follow up.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the end of 1 treatment cycle (after 3 weeks).
    E.5.2Secondary end point(s)
    Part 1
    Secondary:
    On-going evaluation of AEs during treatment and follow up.
    Assessment of PK variables (including Cmax, Cmin, AUC).
    Tumour response evaluation using RECIST 1.1.

    Part 2
    Secondary:
    Assessment of PK variables (including Cmax, Cmin, AUC).
    Assessment of ERK phosphorylation (pERK) in PBMC, skin and tumour biopsies, and assessment of TNF-alpha in plasma.
    Tumour response evaluation using RECIST 1.1.
    E.5.2.1Timepoint(s) of evaluation of this end point
    During treatment and follow up (30 days).
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Dose escalation
    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 Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    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 concerned5
    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 visit last subject
    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
    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: 20
    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 state50
    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)
    Normal treatment for this condition
    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 Decision2012-01-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-01-25
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2014-03-28
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