Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37736   clinical trials with a EudraCT protocol, of which   6184   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).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2010-021082-74
    Sponsor's Protocol Code Number:U31287-A-U201
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-02-21
    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 ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2010-021082-74
    A.3Full title of the trial
    RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND PHASE 1B/2 STUDY OF U3-1287 (AMG 888) IN COMBINATION WITH ERLOTINIB IN EGFR TREATMENT NAÏVE SUBJECTS WITH ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) WHO HAVE PROGRESSED ON AT LEAST ONE PRIOR CHEMOTHERAPY
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized Study comparing placebo and U3-1287 (AMG888) in combination with erlotinib in treatment of subjects with advanced non-small cell lung cancer who have progressed on at least one prior chemotherapy
    A.4.1Sponsor's protocol code numberU31287-A-U201
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01211483
    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 SponsorDAIICHI SANKYO DEVELOPMENT LTD.
    B.1.3.4CountryUnited Kingdom
    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 supportDaiichi Sankyo Pharma Development
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo Development Limited
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street AddressChiltern Place, Chalfont Park
    B.5.3.2Town/ cityGerrards Cross, Buckinghamshire
    B.5.3.3Post codeSL9 0BG
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+441753482800
    B.5.5Fax number+441753899107
    B.5.6E-mailinfo@dsd-eu.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 nameU3-1287 (AMG 888)
    D.3.2Product code U3-1287 (AMG 888)
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 1262787-83-6
    D.3.9.2Current sponsor codeU3-1287
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number70
    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) Yes
    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 Yes
    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
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Treatment for advanced or metastatic NSCLC in combination with erlotinib in subjects who are epidermal growth factor receptor (EGFR) treatment naïve after failure of at least one prior chemotherapy regimen
    E.1.1.1Medical condition in easily understood language
    Non-small cell lung cancer (NSCLC) is a general term for the most common form of solid cancer which affects the lungs.
    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 PT
    E.1.2Classification code 10059515
    E.1.2Term Non-small cell lung cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10029521
    E.1.2Term Non-small cell lung cancer stage IIIB
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase 1b Portion
    - To evaluate the safety and tolerability of the
    combination of U3-1287 (AMG 888) and erlotinib in subjects with advanced or metastatic NSCLC.
    - To determine the recommended dose of U3-1287 (AMG 888) for Phase 2 study (RP2D)in combination with erlotinib.

    Phase II Portion
    - To evaluate progression-free survival (PFS) among all randomized subjects treated with erlotinib in combination with high and low doses of U3-1287 (AMG 888) compared to erlotinib plus placebo.
    - To evaluate the safety profile of the combination of U3-1287 (AMG 888) and erlotinib.
    E.2.2Secondary objectives of the trial
    Phase Ib Portion
    - To assess tumor response of U3-1287 (AMG 888) when combined with erlotinib.
    - To assess the pharmacokinetic (PK) parameters of U3-1287 (AMG 888) when combined with erlotinib.
    Phase II Portion
    - To evaluate overall survival, objective response rate (ORR), duration of response, time to response, time to disease progression, duration of stable disease, and disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) among all randomized subjects treated with erlotinib in combination with high and low doses of U3-1287 (AMG 888) compared to erlotinib plus placebo.
    - To assess the PK parameters of U3-1287 (AMG 888) when combined with erlotinib.
    - To assess the PK parameters of erlotinib when combined with U3-1287 (AMG 888).
    - To evaluate the incidence of HAHA formation (anti-U3-1287 [AMG 888] antibodies).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Men or women ≥ 18 years old.

    2. Histologically or cytologically confirmed NSCLC
    with either:
    − Metastatic disease (Stage IV) OR
    − Stage IIIB disease not amenable to surgery or curative intent.

    3. Disease progression or recurrence following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months) documented by radiographic assessment.

    4. Measurable disease per RECIST guidelines Version 1.1.

    5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

    6. Hematological function, as follows:
    − Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L
    − Platelet count ≥ 100 × 10e9/L
    − Hemoglobin ≥ 9 g/dL.

    7. Renal function, as follows:
    − Calculated creatinine clearance ≥ 60 mL/min using the modified Cockroft-Gault equation or serum creatinine ≤ 1.5 x ULN.

    8. Hepatic function, as follows:
    − Aspartate aminotransferase (AST) ≤ 2.5 ×upper limit of normal (ULN) (if liver
    metastases are present, < 5 × ULN)
    − Alanine aminotransferase (ALT) ≤ 2.5 ×ULN (if liver metastases are present,
    < 5 × ULN)
    − Alkaline phosphatase ≤ 2.5 × ULN (if bone or liver metastases are present, < 5 × ULN)
    − Bilirubin ≤ 1.5 × ULN.

    9. Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 × ULN.

    10. Availability of recent (before treatment start) or archival (does not have to be provided by treatment start) tumor specimen (Phase 2 subjects only).

    11. For female subjects, must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile, or must use maximally effective birth control during the period of therapy, and be willing to use contraception for 6 months following the last investigational drug dose and have a negative urine or serum pregnancy test upon entry into this study if female subjects of childbearing
    potential.

    12. For male subjects, must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug dose.

    13. Subjects must be competent and able to comprehend, sign, and date an Independent Ethics Committee- or Institutional Review Board-approved
    Informed Consent Form (including Health Insurance Portability and Accountability Act
    authorization, if applicable) before performance of any study-specific procedures or tests.
    E.4Principal exclusion criteria
    1. Left ventricular ejection fraction (LVEF) < 45%.

    2. Prior EGFR-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy.

    3. More than 2 prior chemotherapy regimens for this indication (Phase 2 subjects only).

    4. History of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.

    5. History of corneal disease.

    6. History of interstitial lung disease.

    7. Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and require no reatment with steroids may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 4 weeks (2 weeks for subjects with a solitary brain lesion amenable to stereotactic radiosurgery)must have elapsed between the end of radiotherapy and study enrollment.

    8. Uncontrolled hypertension (diastolic > 100 mmHg or systolic > 140 mmHg). It is permissible for the subject to receive treatment with antihypertensive medication to maintain blood pressure within required parameters.

    9. Clinically significant electrocardiogram (ECG) changes that obscure the ability to assess the RR, PR, QT, QTc, and QRS intervals.

    10. Ascites or pleural effusion requiring chronic medical intervention.

    11. Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure (New York Heart Association >Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.

    12. Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment or treatment with small molecule tyrosine kinase inhibitors (TKIs) within 2 weeks before study drug treatment. Prior and concurrent use of hormone replacement therapy is permitted.

    13. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug reatment. Radiation treatment to all sites of measureable disease unless progression is
    documented after radiation. No target lesion should be selected within the reviously irradiated field unless there was progression at that lesion following radiation.

    14. Participated in clinical drug trials within 4 weeks (2 weeks for small molecule TKIs) before study drug treatment. Current participation in other investigational procedures.

    15. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.

    16. History of hypersensitivity to any of the study drugs or to any excipients.

    17. Concurrent use of CYP3A4 inducers or inhibitors.

    18. Any known pre-existing condition including substance abuse that could interfere with subject’s participation in and completion of the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    • Treatment-emergent AEs
    • Clinically significant or ≥ grade 3 events according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 in safety laboratory tests, physical examinations, ECGs, echocardiograms, or vital signs
    • Incidence of DLTs (used to identify RP2D, if applicable) - Phase 1b
    • PFS - Phase 2
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months
    E.5.2Secondary end point(s)
    For both Phase 1b and Phase 2
    · PK parameters (Cmin, Cmax and AUC) of U3-1287 (AMG 888) when combined with erlotinib
    · PK parameters (Cmin, Cmax and AUC) of erlotinib when combined with U3-1287(AMG 888)
    · HAHA profile for U3-1287 (AMG 888)
    · Best overall tumor response
    For Phase 2 only
    · Overall survival (OS)
    · ORR
    · Duration of response
    · Time to response
    · Duration of stable disease (SD)
    · Time to disease progression (TTP)
    · Disease control rate (CR+PR+SD)
    E.5.2.1Timepoint(s) of evaluation of this end point
    12 months
    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 No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    biomarker
    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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA32
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Bulgaria
    Germany
    Hungary
    Israel
    Italy
    Lithuania
    Romania
    Slovenia
    Ukraine
    United Kingdom
    United States
    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
    Refer to protocol
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days30
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days30
    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.1.3Elderly (>=65 years) Yes
    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.4.2 For a multinational trial
    F.4.2.1In the EEA 195
    F.4.2.2In the whole clinical trial 210
    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 Decision2011-04-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-03-10
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2013-12-06
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA