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    Summary
    EudraCT Number:2011-003718-18
    Sponsor's Protocol Code Number:CCR3689
    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:2011-11-22
    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 number2011-003718-18
    A.3Full title of the trial
    Proof-of-concept study of AZD 4547 in patients with FGFR1 or FGFR2 amplified tumours
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of AZD4547 in patients with tumours having high number of copies of the FGFR1 or FGFR2 gene.
    A.3.2Name or abbreviated title of the trial where available
    FGFR
    A.4.1Sponsor's protocol code numberCCR3689
    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 SponsorRoyal Marsden Hospital 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 supportAstra Zeneca Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationThe Royal Marsden Hospital NHS Foundation Trust
    B.5.2Functional name of contact pointAngela Gillbanks
    B.5.3 Address:
    B.5.3.1Street AddressDowns Road
    B.5.3.2Town/ citySutton
    B.5.3.3Post codeSm2 5PT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02086613279
    B.5.5Fax number0208643750
    B.5.6E-mailangela.gillbanks@rmh.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 nameAZD4547
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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
    Advanced Breast Cancer Advanced Lung Cancer Advanced Upper gastrointestinal cancer
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To correlate the anti-tumour activity of AZD4547 with molecular changes on treatment in the FGFR pathway in serial biopsies.
    E.2.2Secondary objectives of the trial
    • To assess the efficacy of AZD4547 in previously treated FGFR1 or FGFR2 amplified breast, lung, or gastro-oesophageal carcinoma • To assess the safety and tolerability of AZD4547 • To assess the pharmacodynamic activity of AZD4547 on FDG-PET scan
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of signed and dated, written informed consent prior to any study specific procedures. 2. Female or male aged 25 years or older. 3. Mandatory provision of archival or fresh tumour biopsy for confirmation of FGFR gene amplification. This must be confirmed by AstraZeneca approved laboratory. 4. World Health Organisation performance status 0-2, minimum life expectancy of 12 weeks from proposed first dose date, no deterioration within 2 weeks of screening and first dose. 5. Patient ability to comply with the collection of tumor biopsies (mandatory at baseline and on days 12-14 6. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with CT or MRI and which is suitable for accurate repeated measurements. ― Local disease confined to the stomach or oesophagus is not considered measurable (patients with locally advanced gastro-oesophageal adenocarcinoma must have at least one measurable nodal lesion ≥15mm in the short axis). 7. Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential. Tumour specific inclusion criteria: Advanced gastro-oesophageal adenocarcinoma ― Histologically proven metastatic or locally advanced inoperable adenocarcinoma of the stomach, lower oesophagus or oesophago-gastric junction. ― Documented progression after 1 or 2 prior courses of chemotherapy for advanced disease, ― FGFR2 amplification as assessed by AZ approved laboratory Advanced breast carcinoma ― Histologically confirmed metastatic or locally advanced breast cancer, negative for HER2 as determined by local laboratory. Patients with locally advanced disease must have recurrent, or progressive, disease that is not suitable for treatment with curative intent ― Patients with ER positive disease must have been treated with at least one line of hormonal therapy for recurrent/progressive disease or have been on hormonal therapy at the time of recurrence/progression ― Documented progression after at least one and no more than three prior courses of chemotherapy regimens for advanced disease. ― FGFR1 or FGFR2 amplification as assessed by AZ approved laboratory. Advanced non-adenocarcinoma lung cancer ― Histologically confirmed metastatic or locally advanced non-adenocarcinoma cell lung carcinoma. ― Documented progression after 1 or 2 prior courses of chemotherapy for advanced disease ― FGFR1 amplification as assessed by AZ approved laboratory
    E.4Principal exclusion criteria
    Patients should not enter the study if any of the following exclusion criteria are fulfilled: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 2. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. 3. Treatment with any of the following: ― Potent inhibitors or inducers of CYP3A4, 2C8 or 2D6 or substrates of CYP3A4 prior to the first dose of study treatment. ― Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment. ― Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks before the first dose of study treatment. ― Prior exposure to AZD4547 5. With the exception of alopecia, any unresolved toxicities from prior therapy with a Common Terminology Criteria for Adverse Events (CTCAE) grade >1 at the time of starting study treatment. 6. Untreated brain metastases (patients with stable brain metastasis, 1 month post treatment are allowed in this study) 7. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 8. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: ― Absolute neutrophil count < 1.5 x 109/L. ― Platelet count < 100 x 109/L. ― Haemoglobin < 90 g/L. ― Alanine aminotransferase > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. ― Aspartate aminotransferase > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases. ― Total bilirubin > 1.5 times ULN. ― Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is > 1.5 times ULN. ― Corrected total calcium > ULN (corrected for albumin using a standard formula that will be specified in the protocol). ― Total phosphate > ULN. 9. Refractory nausea and vomiting, chronic gastrointestinal diseases that would preclude adequate oral intake and absorption of AZD4547. 10. Any of the following cardiac criteria: ― Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 consecutive electrocardiograms (ECGs). ― Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block. ― Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval. 11. Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication. 12. History of hypersensitivity to active or inactive excipients of AZD4547 or other drugs with a similar chemical structure or class to AZD4547. 13. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. 14. Patients with a history of another primary malignancy within 5 years prior to starting study treatment, except adequately treated basal or squamous cell carcinoma of the skin, carcinoma of the cervix in situ and the disease under study. 15. Patients with a history of herpes zoster or active varicella zoster or herpes zoster infection 16. Other concomitant anti-cancer therapy (including LHRH agonists) except steroids. 17. Any of the following ophthalmological criteria: ― Current evidence or previous history of retinal pigmented epithelium detachment ― Previous laser treatment or intra-ocular injection for treatment of macular degeneration ― Current evidence or previous history of dry or wet age-related macular degeneration ― Current evidence or previous history of retinal vein occlusion ― Current evidence or previous history of retinal degenerative diseases (e.g. hereditary) ― Current evidence or previous history of any other clinically relevant chorioretinal defect
    E.5 End points
    E.5.1Primary end point(s)
    • To correlate the anti-tumour activity of AZD4547 with molecular changes on treatment in the FGFR pathway in serial biopsies.
    E.5.1.1Timepoint(s) of evaluation of this end point
    This will be assessed by comparing the anti-tumour activity of AZD4547 on week 8 CT scan with the changes in ERK 1/2 phosphorylation at days 10-14. These analyses will be evaluated at the end of this trial (expected 2 years from start of recruitment).
    E.5.2Secondary end point(s)
    • Objective response rate to AZD4547 in all patients and in each tumour group • Safety and tolerability of AZD4547 • Disease control rate at 8 weeks • Progression free survival in all patients and in each tumour group • To correlate the metabolic changes on FDG-PET scan with molecular changes, circulating tumour cells and structural changes from CT scan.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The response rate to AZD4547 will be evaluated on the CT scans (at 8 weeks and then every 6 weeks thereafter) Disease control rate will be assessed on the CT scan at 8 weeks. The changes on the PET scans will be assessed at day 14 and week 8 from start of treatment. All of these analysis will be performed at the end of this trial (expected 2 years from the start of recruitment).
    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 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) 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
    To correlate anti-tumour efficacy of AZD4547 with molecular changes in the FGFR pathway
    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 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 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
    All patients will be followed up until disease progression to evaluate the secondary end points of the trial. Therefore the ‘end of trial’ for the purposes of the European Clinical Trials Directive will be defined as 30 days after the last patient has had their last active study treatment. The sponsor will inform the MHRA and REC within 90 days of the ‘end of trial’ that the trial has closed.
    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: 50
    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 state48
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 48
    F.4.2.2In the whole clinical trial 48
    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)
    If a patient experiences clinical benefit, the study medication will be continued until disease progression or intolerable side-effects and any continuation of the same treatment beyond this time will not be appropriate.
    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 Decision2011-11-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-02-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-11-30
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    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.

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