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    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   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:2008-005542-23
    Sponsor's Protocol Code Number:CR0708-11
    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:2009-04-28
    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 number2008-005542-23
    A.3Full title of the trial
    A CCLG/Cancer Research UK Phase I Trial of AT9283 (a selective inhibitor of Aurora kinases) given for 72 hours every 21 days via intravenous infusion in children and adolescents with relapsed and refractory solid tumours.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Paediatric study of AT9283 in solid tumours
    A.3.2Name or abbreviated title of the trial where available
    Phase I paediatric study of AT9283 in solid tumours.
    A.4.1Sponsor's protocol code numberCR0708-11
    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 SponsorCancer Research UK
    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.4.1Name of organisation providing supportAstex Therapeutics Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCancer Research UK
    B.5.2Functional name of contact pointCentre for Drug Development (CDD)
    B.5.3 Address:
    B.5.3.1Street AddressAngel Building, 407 St John Street
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeEC1V 4AD
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+4402072420200
    B.5.5Fax number+4402030147633
    B.5.6E-mailregquery@cancer.org.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 nameAT9283 (as the free base of the L-lactate salt)
    D.3.2Product code AT9283 (as the free base of the L-lactate salt)
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAT9283 (as the free base of the L-lactate salt)
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number52
    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
    Relapsed and refractory solid tumours in children and adolescents

    E.1.1.1Medical condition in easily understood language
    Solid tumours
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level LLT
    E.1.2Classification code 10065143
    E.1.2Term Malignant 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
    To evaluate the safety and tolerability of AT9283 (given by intravenous (IV) infusion) by characterising the dose limiting toxicities (DLTs) and determining a maximum tolerated dose (MTD) in children and adolescents with relapsed and refractory solid tumours.
    E.2.2Secondary objectives of the trial
    a) To determine the pharmacokinetics (PK) of AT9283 when administered as an IV infusion in children and adolescents.

    b) To demonstrate the pharmacodynamic (PD) activity of AT9283 in children and adolescents with relapsed/ refractory malignancy by studying its effects in surrogate tissue.

    c) To assess preliminary evidence of activity of AT9283 by using appropriate objective tumour measurements in relapsed/ refractory patients with solid tumours (including central nervous system (CNS) tumours).

    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically proven solid tumour refractory to conventional treatment, or for which no conventional therapy exists.

    Diffuse Intrinsic Pontine Gliomas that have progressed or relapsed after first line therapy can be included without histological verification if they fulfill the following criteria:
    At the time of diagnosis a diffuse intrinsic lesion centred in the pons on MRI imaging with a clinical history of <6 months.
    Diagnostic clinical findings at first presentation must have included at least one of the following three signs of brainstem tumour: (i) cranial nerve deficit (ii) long tract signs, (III)ataxia

    2. Life expectancy of at least 12 weeks.

    3. World Health Organisation (WHO) performance status of 0, 1, or 2 or Lansky Play scale ≥ 70% (a lower score may be acceptable if it is due to a stable neurological deficit and for patients with CNS tumours)

    4. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day -1) before the patient goes on study.

    Laboratory Test Value required
    Haemoglobin (Hb) ≥9.0 g/dl
    Absolute neutrophil count ≥1.0 x 10(9)/L
    Platelet count ≥100 x 10(9)/L
    Creatinine Kinase <ULN
    Serum bilirubin <1.5 x upper limit of normal (ULN)
    Alanine amino-transferase (ALT) or aspartate amino-transferase (AST) < 2.5 x ULN unless raised due to tumour in which case up to 5 x ULN is permissible
    EDTA or DTPA measured Glomerular Filtration Rate (GFR) ≥60 ml/min/1.73 m2

    5. Aged >2 to <19 years

    6. In the investigators opinion, patient has sufficient blood volume to undergo the blood sampling regimen specified by the protocol without jeopardising patient safety.

    7. Written (signed and dated) informed consent from patient and / or parent or legal guardian and be capable of co-operating with treatment and follow-up
    E.4Principal exclusion criteria
    1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous 4 weeks (6 weeks for investigational medicinal products; 2 weeks for vincristine) before treatment.
    Steroids: Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.

    2. Prior exposure to an Aurora kinase inhibitor.

    3. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Centre for Drug Development (CDD) should not exclude the patient.

    4. Pregnant or lactating women are excluded. Female patients with the ability to become pregnant who have a negative serum or urine pregnancy test before enrolment and agree to use two of the following three highly effective forms of combined contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible.

    5. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate.

    6. Major thoracic or abdominal surgery from which the patient has not yet recovered.

    7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection.

    8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).

    9. Fractional shortening of < or = 29% on Echocardiogram

    10. LVEF of <50%

    11. History of allergy or auto-immune disease*.

    12. Congenital heart disease.

    13. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow.

    14. Stem Cell Transplant (SCT): Patients who have undergone an autologous stem cell transplant must be greater than three months from the date of the stem cell return.

    15. Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.

    16. Is a participant or plans to participate in another interventional clinical study, whilst taking part in this Phase I study of AT9283. Participation in an observational study would be acceptable.

    *this criterion is intended to exlude only those patients with a clinically significant history of allergy or auto-immune disease.
    E.5 End points
    E.5.1Primary end point(s)
    1) To determine the Dose Limiting Toxicities (DLT) in children and adolescents with relapsed and refractory solid tumours.

    2) To determine the Maximum Tolerated Dose (as defined by a dose below that at which two or more of up to six patients experience DLT) in children and adolescents with relapsed and refractory solid tumours.

    E.5.1.1Timepoint(s) of evaluation of this end point
    End of trial
    E.5.2Secondary end point(s)
    a) Determining PK parameters and the correlation between them and toxicity and/or efficacy

    b) Determining magnitude and duration of biomarker change following AT9283 administration (M30 and M65 ELISA)

    c) Objective tumour responses using RECIST criteria overall, and if possible according to tumour type and bone marrow examinations, plus disease specific biological markers (e.g. Neuroblastoma- MIBG, catecholamines)
    E.5.2.1Timepoint(s) of evaluation of this end point
    End of trial
    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
    Paediatric
    E.7.2Therapeutic exploratory (Phase II) No
    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.8.3 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 concerned9
    E.8.5The trial involves multiple Member States No
    E.8.5.1Number of sites anticipated in the EEA9
    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 Information not present in EudraCT
    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
    End of the trial is defined as last patient, last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years8
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years8
    E.8.9.2In all countries concerned by the trial months3
    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 Yes
    F.1.1Number of subjects for this age range: 33
    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) Yes
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Paediatrics and adolescents-will obtain assent where possible.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state33
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 33
    F.4.2.2In the whole clinical trial 33
    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)
    As per standard care
    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 Decision2009-06-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-07-27
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-08-30
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