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    The EU Clinical Trials Register currently displays   43977   clinical trials with a EudraCT protocol, of which   7312   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:2020-003512-27
    Sponsor's Protocol Code Number:AIO-YMO/TRK-0120
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2021-08-11
    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 ConcernedGermany - BfArM
    A.2EudraCT number2020-003512-27
    A.3Full title of the trial
    Radiation during Osimertinib Treatment: a Safety and Efficacy Cohort Study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Radiation during Osimertinib Treatment: a Safety and Efficacy Cohort Study
    A.3.2Name or abbreviated title of the trial where available
    ROSE
    A.4.1Sponsor's protocol code numberAIO-YMO/TRK-0120
    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.1.3.4CountryGermany
    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 supportAstraZeneca GmbH
    B.4.2CountryGermany
    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 pointAIO-Studien-gGmbH
    B.5.3 Address:
    B.5.3.1Street AddressKuno-Fischer-Str. 8
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code14057
    B.5.3.4CountryGermany
    B.5.4Telephone number004930814534458
    B.5.5Fax number004930322932926
    B.5.6E-mailaio.regulatory@aio-studien-ggmbh.de
    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.2.1.1.1Trade name Osimertinib
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca
    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.3.1Product nameOsimertinib
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNOsimertinib
    D.3.9.1CAS number 1421373-65-0
    D.3.9.4EV Substance CodeSUB176340
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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 EGFR-mutation positive NSCLC

    The target population will comprise 3 parallel cohorts, for each of which a minimum of 10 subjects is planned to be enrolled:
    1. Irradiation of bone, solid organ (non-lung, non-brain) or soft-tissue metastases
    2. Irradiation of brain metastases (initial lesion size < 3 cm)
    3. Irradiation of lung lesions (primary tumor or metastases, lesion size < 5 cm)
    E.1.1.1Medical condition in easily understood language
    Patients with non-small lung cancer

    patients will be classified in 3 cohorts;
    Irradiation of
    1. bone, solid organ or soft-tissue metastases
    2. brain metastases
    3. lung lesions
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10025064
    E.1.2Term Lung carcinoma
    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 LLT
    E.1.2Classification code 10007096
    E.1.2Term Cancer of lung
    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 21.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    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 21.1
    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.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the safety of osimertinib treatment continuation during irradiation therapy for palliation or oligoprogressive disease by assessment of grade 3-5 AEs during and after concomitant osimertinib and irradiation of tumor sites.
    E.2.2Secondary objectives of the trial
    To assess the efficacy of osimertinib treatment continuation during irradiation therapy for palliation or oligoprogressive disease.
    To investigate Quality of Life during and after irradiation therapy and concomitant osimertinib

    Exploratory objectives
    To investigate types of irradiation (conventional vs. stereotactic) and target volumes used.
    To explore blood- and tissue-based biomarkers in this setting.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of written informed consent prior to any study specific procedures, including screening evaluations that are not SOC.
    2. Age ≥ 18 years at time of study entry.
    3. Histologically confirmed NSCLC
    4. Ongoing or planned osimertinib treatment according to marketing authorization (first line treatment of tumor positive for an activating EGFR mutation, or later line treatment of tumor positive for EGFR T790M mutation, assessed according to local standard. First line therapy is defined as therapy used to treat advanced disease. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy. Experimental therapies when given as separate regimen are considered as separate line of therapy. Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate regimen of therapy.)
    5. Clinical indication for radiotherapy of one or more lesions, for instance for local symptom control of primary tumor or metastasis, for oligoprogressive metastasis, or for disease control with conventional or stereotactic strategy. Radiotherapy of metastatic sites can be for bone, solid organ or soft-tissue lesions; initial size of brain metastases should be < 3 cm. Lung lesions should be no more than 5 cm.
    6. ECOG performance status 0-2.
    7. Life expectancy ≥12 weeks
    8. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test and not be breast-feeding prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
    • Post-menopausal defined as aged 50 years or more and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
    • Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution.
    • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
    • Further information in Section 7.1.1 and Appendix 21.7
    9. Male subjects who are sexually active with WOCBP should be willing to use highly effective contraception (see Section 7.1.1 and Appendix 21.7). Men who are azoospermic do not require contraception.
    10. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.
    11. Negative COVID-19 test within 1 week prior to starting irradiation if clinically required by current regional COVID-19 outbreak situation.
    E.4Principal exclusion criteria
    1. Concurrent enrolment in another clinical study, except observational clinical study, or during the FU of an interventional study
    2. Treatment with an investigational drug within 5 half-lives of the compound or 3 months, whichever is greater
    3. Previous enrolment in the present study
    4. Any chemotherapy, biologic or hormonal cancer therapy other than EGFR-TKIs used concurrently or within 4 weeks prior to study enrolment, or checkpoint inhibitors within 130 days prior to study enrolment. Hormonal therapy for non-cancer-related conditions is acceptable
    5. Any unresolved toxicities from prior therapy greater than grade I which in the investigator’s opinion would jeopardise compliance with the protocol or worsen during irradiation
    6. Cardiac side-effects of osimertinib not sufficiently improved by dose reduction as suggested by the label/ Fachinformation
    7. In patients with indication for radiotherapy of lung lesions: past medical history of ILD/pneumonitis, radiation pneumonitis grade 2 or greater (CTCAE V5.0) or requiring steroid treatment, or any evidence of clinically active ILD, in particular IPF
    8. Major surgery (as defined by the Investigator) within 4 weeks prior to starting the study; patients must have recovered from effects of preceding major surgery.
    9. Congenital long QT syndrome
    10. Any of the following cardiac criteria: Mean resting QTc >470 msec obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG; Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities
    11. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: Absolute neutrophil count <1.5 x 10^9/L; Platelet count <100 x 10^9/L; Hb <90 g/L (9 g/dL); ALT >2.5 times >5 times ULN nin absence or presence of liver metastases resp.; AST >2.5 times or >5 times ULN in absence and presence of liver metastases resp.; Total bilirubin >1.5 times ULN if no liver metastases or >3 times ULN in the presence of documented Gilbert’s Syndrome/liver metastases; Serum creatinine >1.5 times ULN concurrent with creatinine clearance <50 mL/min —confirmation of creatinine clearance is only required when creatinine is >1.5 times ULN
    12. Any evidence of severe or uncontrolled systemic diseases, also uncontrolled hypertension & active bleeding diatheses, which according to the investigator makes the patient undesirable, or active infection
    13. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
    14. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
    15. 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
    16. Active infection will include any patients receiving treatment for infection
    17. Clinical suspicion of COVID-19
    18. Participants with HBV infection are eligible only if they demonstrated absence of HCV co-infection or history of HCV co-infection and absence of HIV infection
    Participants with active HBV infection are eligible if they are receiving anti-viral treatment for at least 6 weeks prior to study treatment, HBV DNA is suppressed to <100 IU/mL and transaminase levels are below ULN.
    Participants with a resolved or chronic HBV infection are eligible if they are negative for HBsAg and positive for hepatitis B core antibody [anti-HBc IgG]. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment or Positive for HBsAg, but for > 6 months have had transaminases levels below ULN and HBV DNA levels <100 IU/mL. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.
    Participants with HIV infection are only eligible if they have undetectable viral RNA load for 6 months, CD4+ count of >350 cells/μL, No history of AIDS-defining opportunistic infection within the past 12 months and Stable for at least 4 weeks on the same anti-HIV medications.
    19. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
    20. Currently receiving medications or herbal that are strong inducers of CYP3A4 (at least 3 week prior)
    21. Women who are pregnant or breast-feeding
    22. Male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 4 months after the last dose of osimertinib
    23. Patients who are unable to consent [§ 40 Abs. 1 S. 3 Nr. 3a AMG]
    E.5 End points
    E.5.1Primary end point(s)
    · Safety and tolerability (Frequency, time of onset and severity of Adverse Events, grading according to CTCAE V5.0), including pneumonitis, interstitial lung disease, radiation pneumonitis, radionecrosis, radiation alveolitis, radiation fibrosis - lung, pulmonary radiation injury and cardiac failure (congestive heart failure – CHF) as adverse events of special interest.
    · Pneumonitis. A consensus definition of pneumonitis based on symptoms, clinical examination, imaging and pulmonary function testing, as well as any available bronchoscopy results, will be used. In the absence of bronchoscopy, pharyngeal wash should be used to exclude viral infections.
    Care should be taken to differentiate between drug-induced and radiation-induced pneumonitis, by taking into account the localization (in-field or outside irradiated area) and time of onset relative to treatment.
    Pneumonitis severity is defined according to CTCAE V5.0:
    Grade 1 Asymptomatic; clinical or diagnostic observations only; intervention not indicated
    Grade 2 Symptomatic; medical intervention indicated; limiting instrumental ADL
    Grade 3 Severe symptoms; limiting self care ADL; oxygen indicated
    Grade 4 Life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation)
    Grade 5 Death
    · Radionecrosis: A consensus definition of radionecrosis based on imaging and clinical consultation will be used
    E.5.1.1Timepoint(s) of evaluation of this end point
    Continuously up to 12 months after completion of treatment phase
    E.5.2Secondary end point(s)
    • Progression-free survival (PFS), calculated as PFS1, PFS2, PFS3, PFS0 to assess osimertinib treatment continued beyond several progression events entailing radiotherapy, and prior to first radiotherapy
    • Time to treatment failure (TTF)
    • Local tumor control
    • Overall survival (OS)
    • Quality of Life assessed by EORTC QLQ-C30

    Exploratory analysis / translational research endpoints
    • Blood sample analysis and biomarker assessment
    • Optional tumor tissue analysis (pre-study FFPE sample) and biomarker correlation with patient baseline characteristics and outcomes
    • Target volume of irradiation
    • Type of irradiation (conventional, stereotactic)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Continuously up to 12 months after completion of treatment phase
    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 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.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 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 Yes
    E.8.1.7.1Other trial design description
    Single arm, explorative, multi-center parallel cohort study
    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.8.2.4Number of treatment arms in the trial1
    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 concerned10
    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
    End of Study (EoS) is defined as the time-point when the last subject has completed a 12-month follow-up period.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months60
    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: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 state40
    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)
    The patients will be treated according to their health status and according to standard of 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 Decision2021-11-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-12-08
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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