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    The EU Clinical Trials Register currently displays   43845   clinical trials with a EudraCT protocol, of which   7282   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:2019-001155-39
    Sponsor's Protocol Code Number:CO40778
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2019-07-25
    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 ConcernedFrance - ANSM
    A.2EudraCT number2019-001155-39
    A.3Full title of the trial
    A PHASE 1/2, OPEN-LABEL, DOSE-ESCALATION AND EXPANSION STUDY OF ENTRECTINIB (RXDX-101) IN PEDIATRICS AND YOUNG ADULTS WITH NO CURATIVE FIRST-LINE TREATMENT OPTION OR RECURRENT/REFRACTORY SOLID TUMORS AND PRIMARY CNS TUMORS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Entrectinib (RXDX-101) in Pediatrics and Young Adults with No Curative First-Line Treatment Option or Recurrent/Refractory Solid Tumors and Primary CNS Tumors
    A.4.1Sponsor's protocol code numberCO40778
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/010/2019
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffman-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 nameEntrectinib
    D.3.2Product code RO7102122
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation Yes
    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 INNENTRECTINIB
    D.3.9.1CAS number 1108743-60-7
    D.3.9.2Current sponsor codeRO7102122
    D.3.9.4EV Substance CodeSUB177830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 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 nameEntrectinib
    D.3.2Product code RO7102122
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation Yes
    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 INNENTRECTINIB
    D.3.9.1CAS number 1108743-60-7
    D.3.9.2Current sponsor codeRO7102122
    D.3.9.4EV Substance CodeSUB177830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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
    Solid tumors and primary central nervous system (CNS) tumors
    E.1.1.1Medical condition in easily understood language
    A solid tumor is an abnormal tissue mass that arises from uncontrolled growth of cells and spreads locally or to other parts of the body and one that starts in brain is called a primary brain tumor
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065147
    E.1.2Term Malignant solid tumor
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065252
    E.1.2Term Solid tumor
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D), of entrectinib in pediatric patients (pediatrics and young adults) with relapsed or refractory solid tumors (Part A)
    • To evaluate efficacy of entrectinib as assessed by objective response rate (ORR) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 molecular alterations (Part B) using Response Assessment in Neuro-Oncology Criteria (RANO) and in patients with extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions (Part D) using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), as assessed by blinded independent central review (BICR)
    E.2.2Secondary objectives of the trial
    • To describe the safety profile of entrectinib
    • To characterize the PK of entrectinib
    • To determine the duration of response (DOR), time to response (TTR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS) in all enrolled patients receiving entrectinib at the RP2D
    • To determine the intracranial tumor response, DOR, TTR, and CNS- PFS in Parts B and D patients receiving entrectinib at the RP2D and presenting with measurable primary or secondary CNS disease at baseline, using RANO or RANO-BM, as applicable
    • To describe growth, puberty, neurological and neurocognitive function of patients on treatment
    • To evaluate the efficacy of entrectinib as assessed by ORR in all patients with NTRK1/2/3 gene fusions, regardless of study phase or cohorts using RANO for CNS tumors or RECIST v1.1 for extra-cranial tumors, as assessed by BICR
    • To characterize palatability and tolerability of the age-appropriate formulation
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Body surface area (BSA): Patients must have a BSA >= 0.43 m2 at the time of the study enrollment
    Disease status:
    - Phase 1 portion: Patients must have measurable or evaluable disease
    - Phase 2 portion:
    – Part B, Part D, Part C: Patients must have measurable or evaluable disease
    – Part E: Patients must have measurable or evaluable disease and will be assessed according to tumor type
    - Tumor types included below harboring NTRK1/2/3 or ROS1 gene fusions as determined locally by an appropriately validated assay performed in a Clinical Laboratory Improvement Amendments-certified or equivalently-accredited diagnostic laboratory, or centrally by a Foundation Medicine Clinical Trial Assay:
    o Phase 1 portion:
    – Part A: Relapsed or refractory extracranial solid tumors
    o Phase 2 portion:
    – Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions
    – Part D: Extracranial solid tumors with NTRK1/2/3 or ROS1 gene fusions
    - Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
    - For patients enrolled via local molecular testing, an archival tumor tissue from diagnosis or, preferably, from relapsed disease is required to be submitted for independent central testing at Foundation Medicine, Inc. laboratory
    - Age: Male or female from birth to age < 22 years
    - Performance status: Lansky or Karnofsky score >= 60% and minimum life expectancy of at least 4 weeks
    - Prior therapy: The patient’s cancer must have no curative first-line treatment option or recurrent/refractory solid tumors and primary CNS tumors. Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
    - Adequate bone marrow, liver, renal, cardiac and neurologic function
    - Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation and in the following 90 days after discontinuation of study treatment
    - Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
    E.4Principal exclusion criteria
    - Current participation in another therapeutic clinical trial
    - Known congenital long QT syndrome
    - Known active infections (bacterial, fungal, or viral)
    - Receiving Enzyme Inducing Antiepileptic Drugs within prior 14 days
    - All Phase 2 patients: Prior treatment with approved or investigational tyrosine receptor kinase inhibitor (TRK) or ROS1 inhibitors
    - Patients with NB with bone marrow space-only disease
    - Incomplete recovery from acute effects of any surgery prior to treatment
    - Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption
    - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or entrectinib administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry in to this study or could compromise protocol objectives in the opinion of the Investigator and/or Sponsor
    E.5 End points
    E.5.1Primary end point(s)
    1. Dose limiting toxicity of entrectinib (Part A)
    2. Objective response rate (Part B)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Day 1-28 of Cycle 1
    2. Up to 30 days after last dose of study drug
    E.5.2Secondary end point(s)
    1. Incidence and severity of adverse events, laboratory and electrocardiogram (ECG) abnormalities
    2. Maximal plasma concentration (Cmax) of entrectinib
    3. Time of maximal plasma concentration (Tmax) of entrectinib
    4. Area under the plasma concentration vs. time curve (AUC) of entrectinib
    5. Duration of response in patients with relapsed or refractory extracranial solid tumors
    6. Time to response in patients with relapsed or refractory extracranial solid tumors
    7. Clinical benefit rate in patients with relapsed or refractory extracranial solid tumors
    8. Progression-free survival in patients with relapsed or refractory extracranial solid tumors
    9. Intracranial tumor response in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    10. Duration of response in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    11. Time to response in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    12. CNS- Progression-free survival in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    13. Overall survival for all patients
    14. Objective response rate in all patients
    15. Acceptability and palatability assessment for capsules and age-appropriate dosage form
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to 30 days after last dose and every 3 months until death
    2-4. Cycle 1 Day 1 pre-dose and at 1, 2, 4, 6, and 24 hours post-dose; Cycle 1 Days 8, 15 and 22 pre-dose; on Cycle 2 Day 1 pre-dose and at 1, 2, 4, 6, and 24 hours post-dose; and on Day 1 of every cycle thereafter pre-dose
    5- 14. Up to 30 days after last dose of the study drug and every 3 months until death
    15. Day 1 of Cycle 1
    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 Yes
    E.6.13.1Other scope of the trial description
    Determine Maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D), of entrectinib in paediatric patients.
    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 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 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    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
    France
    Germany
    Italy
    Spain
    United Kingdom
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years11
    E.8.9.2In all countries concerned by the trial months1
    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: 50
    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) Yes
    F.1.1.5.1Number of subjects for this age range: 25
    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: 18
    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 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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Young children under the age of 18.
    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 14
    F.4.2.2In the whole clinical trial 68
    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)
    None
    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 Decision2019-09-16
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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