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    Summary
    EudraCT Number:2019-000212-28
    Sponsor's Protocol Code Number:LOXO-RET-18036
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-09-04
    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 number2019-000212-28
    A.3Full title of the trial
    A Phase 1/2 Study of the Oral RET Inhibitor LOXO-292 in Pediatric Patients with Advanced RET-Altered Solid or Primary Central Nervous System Tumors
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 1/2 Study on the effects of the LOXO-292 (study drug) in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors
    A.4.1Sponsor's protocol code numberLOXO-RET-18036
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03899792
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/369/2019
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorLoxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company
    B.1.3.4CountryUnited States
    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 supportLoxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedpace
    B.5.2Functional name of contact pointClinical Trial Information
    B.5.3 Address:
    B.5.3.1Street Addressul. ┼╗wirki i Wigury 16C
    B.5.3.2Town/ cityWarsaw
    B.5.3.3Post code02-092
    B.5.3.4CountryPoland
    B.5.6E-mailregsubmissions@medpace.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2071
    D.3 Description of the IMP
    D.3.1Product nameSelpercatinib
    D.3.2Product code LOXO-292
    D.3.4Pharmaceutical form Capsule, hard
    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 INNSelpercatinib
    D.3.9.1CAS number 2152628-30-1
    D.3.9.2Current sponsor codeLOXO-292
    D.3.9.3Other descriptive nameSelpercatinib
    D.3.9.4EV Substance CodeSUB193120
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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.IMP: 2
    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 RETEVMO
    D.2.1.1.2Name of the Marketing Authorisation holderLoxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2071
    D.3 Description of the IMP
    D.3.1Product nameSelpercatinib
    D.3.2Product code LOXO-292
    D.3.4Pharmaceutical form Capsule, hard
    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 INNSelpercatinib
    D.3.9.1CAS number 2152628-30-1
    D.3.9.2Current sponsor codeLOXO-292
    D.3.9.3Other descriptive nameSelpercatinib
    D.3.9.4EV Substance CodeSUB193120
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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.IMP: 3
    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 RETEVMO
    D.2.1.1.2Name of the Marketing Authorisation holderLoxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2071
    D.3 Description of the IMP
    D.3.1Product nameSelpercatinib
    D.3.2Product code LOXO-292
    D.3.4Pharmaceutical form Capsule, hard
    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 INNSelpercatinib
    D.3.9.1CAS number 2152628-30-1
    D.3.9.2Current sponsor codeLOXO-292
    D.3.9.3Other descriptive nameSelpercatinib
    D.3.9.4EV Substance CodeSUB193120
    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.IMP: 4
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/18/2071
    D.3 Description of the IMP
    D.3.1Product nameSelpercatinib
    D.3.2Product code LOXO-292
    D.3.4Pharmaceutical form Powder for oral suspension
    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 INNSelpercatinib
    D.3.9.1CAS number 2152628-30-1
    D.3.9.2Current sponsor codeLOXO-292
    D.3.9.3Other descriptive nameSelpercatinib
    D.3.9.4EV Substance CodeSUB193120
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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
    Pediatric Patients with Advanced RET-Altered Solid or Primary Central Nervous System Tumors
    E.1.1.1Medical condition in easily understood language
    Pediatric patients with an activating RET alteration and an advanced solid or primary Central Nervous System (CNS) Tumors
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10007958
    E.1.2Term Central nervous system neoplasm
    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 21.0
    E.1.2Level LLT
    E.1.2Classification code 10007959
    E.1.2Term Central nervous system neoplasm NOS
    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 21.0
    E.1.2Level LLT
    E.1.2Classification code 10049516
    E.1.2Term Malignant tumor
    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 20.1
    E.1.2Level HLT
    E.1.2Classification code 10007960
    E.1.2Term Central nervous system neoplasms malignant NEC
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10027105
    E.1.2Term Medullary thyroid cancer
    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 1
    The primary objective is to determine the safety profile, including dose-limiting toxicities (DLTs), of the oral RET inhibitor Selpercatinib

    PHASE 2
    To determine the objective response rate (ORR) as determined by an Independent Review Committee (IRC) and measured by the proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors, version 1.1(RECIST v 1.1), or Response Assessment in Neuro-Oncology (RANO) criteria, as appropriate, following treatment with Selpercatinib
    E.2.2Secondary objectives of the trial
    PHASE1
    •characterize Selpercatinib PK properties
    •identify MTD and/or the RP2D Selpercatinib dose
    •describe Selpercatinib antitumor activity
    •evaluate changes from baseline in pain and HRQoL measures assessed by Wong-Baker Faces Scale and PedsQL
    PHASE2
    •determine:
    -ORR using RECIST1.1 or RANO criteria
    -DOR in patients with best overall response of CR or PR
    -PFS duration following Selpercatinib initiation
    -OS following Selpercatinib initiation
    -CBR based on proportion of patients with best overall response of CR, PR or stable disease lasting ≥ 16 weeks
    •assess Selpercatinib safety profile, tolerability
    •characterize Selpercatinib PK properties
    •evaluate concordance of prior molecular profiling detected an activating RET alteration within the tumor
    •characterize post-operative staging and surgical margin status in patients who have definitive surgery following Selpercatinib treatment
    •describe putative pretreatment surgical plan and capture post treatment actual approach
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Pediatric patients ≥ 12 years of age and ≤ 21 years of age at Cycle 1 Day 1 (C1D1) with a locally advanced or metastatic solid or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and/or for which no standard or available systemic curative therapy exists.
    a) Patients with locally advanced disease who would require, in the opinion of the Investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection, are also eligible.
    2. Evidence of an activating RET gene alteration in tumor and/or blood as identified through molecular assays, as performed for clinical evaluation.
    3. Patients with primary CNS tumors or cerebral metastasis:
    a) Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment
    b) Must have not required increasing doses of steroids within the 7 days prior to enrollment to manage CNS symptoms
    4. Imaging study must be performed within 28 days of C1D1 while on stable dose steroid medication (if needed) for at least 7 days immediately before the imaging study.
    5. Histologic verification of malignancy at original diagnosis or relapse, except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebral spinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG).
    6. Must have measurable or non-measurable disease.
    7. Karnofsky (patients 16 years and older) or Lansky (patients younger than 16 years) performance score of at least 50.
    8. Must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy to CTCAE (v5.0) Grade ≤ 2.
    9. An archival (FFPE or fresh frozen) or fresh tumor tissue sample must be available (refer to Section 7.5 of the protocol).
    10. Adequate hematologic/pancreatic status, defined as:
    a) Absolute neutrophil count (ANC) ≥ 1.0× 10^9/L not requiring growth factor support for at least 7 days prior to treatment.
    b) Platelet count ≥ 75 × 10^9/L not requiring transfusion support for at least 7 days prior to treatment.
    c) Hb ≥ 8 mg/dL not requiring transfusion support or erythropoietin for at least 7 days prior to treatment.
    11. Adequate hepatic/pancreatic function, defined as:
    a) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 × the upper limit of normal (ULN) or ≤ 5 × ULN with documented liver involvement (such as liver metastasis or a primary biliary tumor), and
    b) Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN with documented liver involvement or Gilbert’s Disease (patients with Gilbert’s Disease may be enrolled with prior Sponsor approval), and
    c) Pancreatic lipase ≤ 1.5 × ULN (or Sponsor’s approval).
    12. Adequate renal function, defined as:
    a) Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 based on local institutional practice for determination, or a maximum serum creatinine by age and gender as presented in Synopsis Table 3.
    13. Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
    14. Willingness of male and female patients with reproductive potential to utilize double effective birth control methods
    15. Ability to swallow capsules, liquid suspension, or gastric access via a naso- or gastric tube.
    16. Parent/guardian of child or adolescent patient has the ability to understand, agree to, and sign the study Informed Consent Form (ICF) and applicable Pediatric Assent Form before initiation of any protocol-related procedures; patient has the ability to give assent, as applicable, at the time of parental/guardian consent.
    17. Life expectancy of at least 3 months.
    E.4Principal exclusion criteria
    1. Major surgery within 4 weeks prior to C1D1.
    2. Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolonged QT interval corrected for heart rate (QTc) interval > 440 milliseconds for patients ≤ 15 years old and > 470 milliseconds for patients > 15 years old. For patients ≤ 15 years old, Bazett’s Formula will be utilized to determine QTc. For patients > 15 years old, either method, Fridericia or Bazett’s Formula may be applied.
    3. Active uncontrolled systemic bacterial, viral, or fungal infection, which in the opinion of the Investigator makes the risk: benefit ratio for the patient to participate in the trial unfavorable.
    4. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
    5. Pregnancy or lactation.
    6. Uncontrolled hypotension or hypertension ≥ Grade 3 CTCAE (v 5.0).
    7. Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the patient required a modification to current thyroid medication in the 7 days before start of selpercatinib).
    8. Uncontrolled symptomatic hypercalcemia or hypocalcemia.
    9. Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (refer to Appendix D of the main protocol for examples).
    10. Known hypersensitivity to any of the components of the investigational agent, selpercatinib or Ora-Sweet® SF and OraPlus®, for patients who will receive selpercatinib suspension.
    11. Current treatment with proton pump inhibitors (PPIs).
    12. Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s]).
    Note: Patients who discontinue another selective RET inhibitor(s) due to intolerance may be eligible with prior Sponsor approval.
    E.5 End points
    E.5.1Primary end point(s)
    PHASE 1
    1. Frequency, severity and relatedness of TEAEs and SAEs, including DLTs in pediatric patients receiving selpercatinib

    PHASE 2
    1. ORR based on RECIST v 1.1 or RANO as appropriate to tumor type as determined by an IRC
    E.5.1.1Timepoint(s) of evaluation of this end point
    PHASE 1:
    1. From the time of informed consent, for approx.24 months (or earlier if the patient discontinues from the study), and through Safety FU (28 days after the last dose). DLTs during the first 28-day cycle of selpercatinib treatment

    PHASE 2:
    1. approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed.
    E.5.2Secondary end point(s)
    PHASE 1:
    1. Plasma concentrations of selpercatinib and PK parameters, including, but not limited to area under the concentration versus time curve from time 0 to 24 hours (AUC0-24), maximum drug concentration (Cmax), time to maximum plasma concentration (Tmax), degree of accumulation, and other characterizations
    2. To identify the MTD and/or the RP2D of selpercatinib in pediatric patients
    3. To describe the antitumor activity of selpercatinib in pediatric patients with tumors harboring an activating RET alteration
    4. Changes from baseline in pain scales and PedsQL-Core scores

    PHASE 2
    1. ORR based on RECIST v 1.1 or RANO as appropriate to tumor type per the treating Investigator’s response assessment
    2. DOR (IRC and treating Investigator)
    3. PFS (IRC and treating Investigator)
    4. OS
    5. CBR (IRC and treating Investigator)
    6. Frequency, severity, and relatedness of TEAEs and SAEs, changes in hematology and blood chemistry values, and assessments of physical examinations, vital signs, and ECGs
    7. Concordance rate of prior molecular profiling that detected a RET alteration within the patient’s tumor with diagnostic tests being evaluated by the Sponsor
    8. Post-operative staging and surgical margin status in patients who have definitive surgery following treatment with selpercatinib
    9. Number of patients with putative pretreatment surgical plan and the actual post treatment approach with an emphasis on the functional and cosmetic outcome
    E.5.2.1Timepoint(s) of evaluation of this end point
    PHASE 1:
    1.Day 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation
    2.MTD:Day 1 & 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-patient Dose Escalation
    2.RP2D: first 28 days of treatment (Cycle1) and every cycle for approx.12 months
    3.Approx.every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in patients who have not progressed
    4.Up to 24 months

    PHASE 2:
    1-5.Approx. every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in patients who have not progressed.
    6.From the time of informed consent, for approx.24 months (or earlier if the patient discontinues from the study), and through Safety FU (28 days after the last dose)
    7. 6months
    8. 6months
    9. 6months
    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 Yes
    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
    Dose escalation
    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.8.2.4Number of treatment arms in the trial1
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA5
    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
    Australia
    Canada
    Denmark
    France
    Germany
    Italy
    Japan
    Spain
    United States
    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
    Individual patients will continue dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. It is anticipated that a patient on this study will receive treatment with open-label selpercatinib until the patient is able to obtain commercially available selpercatinib in their respective country, the patient does not meet criteria requiring discontinuation of treatment, and the patient’s participation in the study has not ended.
    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 months7
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    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 Yes
    F.1.1Number of subjects for this age range: 73
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 6
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 42
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 25
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 17
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 25
    F.4.2.2In the whole clinical trial 90
    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 treatment discontinuation, Long-Term Follow-up (LTFU) assessments and procedures will be conducted in accordance with the Schedule of Assessments (Protocol, Table 11-1). LTFU will occur approximately every 3 months (±1 month) until the patient experiences PD, withdraws consent for further participation, is lost to follow-up, has died, or close of the study.
    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 Decision2020-01-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-12-17
    P. End of Trial
    P.End of Trial StatusOngoing
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