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    The EU Clinical Trials Register currently displays   36645   clinical trials with a EudraCT protocol, of which   6051   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.
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    EudraCT Number:2017-000105-20
    Sponsor's Protocol Code Number:0316-ASG
    National Competent Authority:Germany - PEI
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-04-11
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedGermany - PEI
    A.2EudraCT number2017-000105-20
    A.3Full title of the trial
    Neoadjuvant anti PD-1 immunotherapy in resectable non-small cell lung cancer
    Neoadjuvante anti-PD-1 Immuntherapie bei operablem nichtkleinzelligen
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Administration of an anti-cancer therapy, which is based on release of brakes in the natural immune response, in patients which are planned to subsequently undergo surgery for removal of their non-small cell lung cancer
    Verabreichung einer Krebs-Therapie, welche auf dem Lösen von Bremsen der natürlichen Körperabwehr basiert, bei Patienten deren nichtkleinzelliger Lungenkrebs anschließend in einer Operation entfernt werden soll
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code number0316-ASG
    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 SponsorAIO-Studien-gGmbH
    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 supportMSD SHARP & DOHME GMBH
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAIO-Studien-gGmbH
    B.5.2Functional name of contact pointDr. Aysun Karatas
    B.5.3 Address:
    B.5.3.1Street AddressKuno-Fischer-Straße 8
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code14057
    B.5.4Telephone number004930814534431
    B.5.5Fax number004930322932926
    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 Yes
    D. name Keytruda
    D. of the Marketing Authorisation holderMerck Sharp & Dohme Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.4Pharmaceutical form 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.3.8INN - Proposed INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.3Other descriptive nameMK-3475
    D.3.9.4EV Substance CodeSUB91641
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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) Yes
    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
    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 (NSCLC), resectable
    E.1.1.1Medical condition in easily understood language
    non-small cell lung cancer (NSCLC), removable by surgery
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10029520
    E.1.2Term Non-small cell lung cancer stage IIIA
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10029518
    E.1.2Term Non-small cell lung cancer stage II
    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
    - feasibility and safety of a neoadjuvant application of pembrolizumab
    - antitumor activity of pembrolizumab with regard to clinical and pathologic tumor response
    E.2.2Secondary objectives of the trial
    - impact of neoadjuvant pembrolizumab on patient survival
    - explore potential predictive biomarkers for pembrolizumab efficacy
    - immune cell imaging
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Cooperation and willingness to complete all aspects of the study
    2. Signed and dated written informed consent must be given prior to study inclusion
    3. Histological or cytological confirmed NSCLC.
    4. Clinical stage II-IIIA according to the TNM classification, 7th edition.
    stage IIIa: T1/T2 N2 (IIIa1-3 Robinson classification)
    5. Adequate disease staging by PET/CT performed and resectability established.
    6. At least 1 measurable lesion according to RECIST 1.1
    7. Age ≥ 18 years
    8. ECOG performance status 0 - 1
    9. Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in in the protocol, for the course of the study through 120 days after the last dose of study medication.
    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
    Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    10. Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in protocol, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
    11. Adequate bone marrow function, liver and renal function:
    a. Absolute neutrophil count ≥ 1.5 x 10^9/L
    b. Thrombocytes ≥ 100 x 10^9/L
    c. Hemoglobin ≥ 9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
    d. INR < 1.4 ULN and PTT < 40 seconds during the last 7 days before therapy
    e. Bilirubin < 1.5 x upper limit of normal
    f. AST (GOT) and ALT (GPT) < 2.5 x ULN
    g. Albumin ≥ 2.5 mg/dL
    h. Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl):
    ≤1.5 X upper limit of normal (ULN) OR
    ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
    12. Adequate lung and cardiac function for intended lung resection according to German S3 guideline
    E.4Principal exclusion criteria
    1. Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery
    2. Participation in a clinical trial within the last 30 days prior to study treatment
    3. History of allogeneic tissue/solid organ transplant
    4. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
    5. Evidence of interstitial lung disease.
    6. cT4 tumor
    7. Symptomatic acute cardiovascular or cerebrovascular disease
    8. Known active HBV, HCV or HIV infection
    9. Has any other active infection requiring systemic therapy.
    10. Patients with active tuberculosis
    11. Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-Programmed cell death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor [TNFR] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
    12. A diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
    13. Patient has had a prior monoclonal antibody within 4 weeks prior to study Day 1
    14. Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. [Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, he/she must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.]
    15. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s syndrome will not be excluded from the study.
    16. Has received a live vaccine within 30 days prior to the first dose of trial treatment. [Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.]
    17. Has known hypersensitivity to pembrolizumab or any of constituents of the product.
    18. Other active malignancy requiring treatment
    Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
    19. Lactating or pregnant women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner). Women of childbearing potential must have a negative pregnancy test (serum β-hCG) at Screening.
    20. Any psychiatric illness that would affect the patient’s ability to understand the demands of the clinical trial
    21. Patient has already been recruited in this trial
    22. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
    23. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
    E.5 End points
    E.5.1Primary end point(s)
    The trial design will be a phase II trial, with descriptive outcome assessments of:
    • frequency and severity of adverse events including peri- and post-operative complications (grade 2-4 AEs according to NCI-CTCAE V4.03)
    • number of patients treated in compliance with protocol
    • Tumor response evaluation
    Clinical response parameters:
    o response rates (∆ tumor size / lymph node size), according to RECIST 1.1 criteria
    o ∆ PET-activity (standardized uptake value [SUV])
    Pathologic response parameters:
    o Pathologic regression grading according to Junker criteria
    E.5.1.1Timepoint(s) of evaluation of this end point
    after relevant data for the respective endpoint has been collected and cleaned or at the end of study
    E.5.2Secondary end point(s)
    • disease free survival
    • overall survival
    • prognostic value of tumor shrinkage
    • prognostic value of inflammatory infiltrates in and around the resected tumor
    • serum- and tumor tissue cytokine concentrations
    • multi-OMICS tissue analysis approach for markers and mechanisms
    E.5.2.1Timepoint(s) of evaluation of this end point
    after relevant data for the respective endpoint has been collected and cleaned or at the end of study
    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. 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 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 Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    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
    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 months10
    E.8.9.1In the Member State concerned days
    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: 15
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    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 state30
    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)
    After completion of study at the End-of-Treatment-Visit, patients will generally be treated at the discretion of the investigator according to medical routine.
    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 Decision2017-08-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-10-02
    P. End of Trial
    P.End of Trial StatusOngoing
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