Evidence map›Paper›PMID 28605510›Full record

Trial reportNeuro-oncology2017

Phase I study of oral sonidegib (LDE225) in pediatric brain and solid tumors and a phase II study in children and adults with relapsed medulloblastoma.

Mark W Kieran, Julia Chisholm, Michela Casanova, Alba A Brandes, Isabelle Aerts, Eric Bouffet, Simon Bailey, Sarah Leary, Tobey J MacDonald, Francoise Mechinaud and 9 more

Open access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neuro-oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

111 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.

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  11. National multicentered retrospective review of salvage therapy for pediatric medulloblastoma: a Canadian experience.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025
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51 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 3 countries.

Mark W KieranPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Julia ChisholmPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Michela CasanovaPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Alba A BrandesPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Isabelle AertsPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Eric BouffetPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Simon BaileyPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Sarah LearyPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Tobey J MacDonaldPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Francoise MechinaudPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Kenneth J CohenPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Riccardo RiccardiPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Warren MasonPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Darren HargravePediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Stacey Kalambakas
Priya DeshpandePediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Feng TaiPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Eunju Hurh
Birgit GeoergerPediatric Neuro-Oncology, Dana-Farber Boston Children's Cancer Blood Disorders Center, Harvard Medical School, Boston, Massachusetts, USA; The Royal Marsden Hospital, Sutton, Surrey, UK; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Medical Oncology, Azienda USL-IRCCS Institute of Neurological Science, Bologna, Italy; Institut Curie and University Paris Descartes, Paris, France; Division of Haematology/Oncology at The Hospital for Sick Children, Toronto, Ontario, Canada; Sir James Spence Institute of Child Health Royal Victoria Infirmary, Newcastle, UK; Seattle Children's Hospital, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA; The Royal Children's Hospital, Children's Cancer Center, Melbourne, Australia; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA; Catholic University of the Sacred Heart, Rome, Italy; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Paediatric Oncology Unit, Great Ormond Street Hospital, London, UK; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; Gustave Roussy, Department of Pediatric and Adolescent Oncology, University Paris-Sud, Université Paris-Saclay, Villejuif, France.
Institut Curie · FRJohns Hopkins University · USCancer Clinic · USPrincess Margaret Cancer Centre · CAUniversité Paris-Saclay · FRChildren's Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSonidegib (LDE225) is a potent, selective hedgehog (Hh) inhibitor of Smoothened. This study explored the safety and pharmacokinetics of sonidegib in children with relapsed/recurrent tumors followed by a phase II trial in pediatric and adult patients with relapsed medulloblastoma (MB) to assess tumor response.

methodsPediatric patients aged ≥1 to <18 years were included according to a Bayesian design starting at 372 mg/m2 of continuous once daily oral sonidegib. Tumor samples were analyzed for Hh pathway activation using a validated 5-gene Hh signature assay. In phase II, pediatric patients were treated at the recommended phase II dose (RP2D) while adults received 800 mg daily.

resultsSixteen adult (16 MB) and 60 pediatric (39 MB, 21 other) patients with an age range of 2-17 years were enrolled. The RP2D of sonidegib in pediatric patients was established at 680 mg/m2 once daily. The phase II study was closed prematurely. The 5-gene Hh signature assay showed that the 4 complete responders (2 pediatric and 2 adult) and 1 partial responder (adult) all had Hh-activated tumors, while 5 patients with activated Hh had either stable disease (n = 3) or progressive disease (n = 2). No patient with an Hh-negative signature (n = 50) responded. The safety profile for pediatric patients was generally consistent with the one established for adult patients; however, growth plate changes were observed in prepubertal pediatric patients.

conclusionsSonidegib was well tolerated and the RP2D in pediatric patients was 680 mg/m2 once daily. Five of the 10 MB patients with activated Hh pathway demonstrated complete or partial responses.

Indexed as

Administration, OralAdolescentAdultAgedBiphenyl CompoundsBrain NeoplasmsCerebellar NeoplasmsChildChild, PreschoolFemaleFollow-Up StudiesHumansMaleMedulloblastomaMiddle AgedNeoplasm Recurrence, LocalBiphenyl CompoundsPyridinessonidegibclinical trialmedulloblastomaPTCHSMOsonic hedgehog

Identifiers

PMID28605510
PMCPMC5737275
OpenAlexW2622523903

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