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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.

Identifieur interne : 000433 ( PubMed/Corpus ); précédent : 000432; suivant : 000434

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.

Auteurs : Mark W. Kieran ; Julia Chisholm ; Michela Casanova ; Alba A. Brandes ; Isabelle Aerts ; Eric Bouffet ; Simon Bailey ; Sarah Leary ; Tobey J. Macdonald ; Francoise Mechinaud ; Kenneth J. Cohen ; Riccardo Riccardi ; Warren Mason ; Darren Hargrave ; Stacey Kalambakas ; Priya Deshpande ; Feng Tai ; Eunju Hurh ; Birgit Geoerger

Source :

RBID : pubmed:28605510

Abstract

Sonidegib (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.

DOI: 10.1093/neuonc/nox109
PubMed: 28605510

Links to Exploration step

pubmed:28605510

Le document en format XML

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<name sortKey="Kieran, Mark W" sort="Kieran, Mark W" uniqKey="Kieran M" first="Mark W" last="Kieran">Mark W. Kieran</name>
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<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<name sortKey="Chisholm, Julia" sort="Chisholm, Julia" uniqKey="Chisholm J" first="Julia" last="Chisholm">Julia Chisholm</name>
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<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<name sortKey="Casanova, Michela" sort="Casanova, Michela" uniqKey="Casanova M" first="Michela" last="Casanova">Michela Casanova</name>
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<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<name sortKey="Brandes, Alba A" sort="Brandes, Alba A" uniqKey="Brandes A" first="Alba A" last="Brandes">Alba A. Brandes</name>
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<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<name sortKey="Aerts, Isabelle" sort="Aerts, Isabelle" uniqKey="Aerts I" first="Isabelle" last="Aerts">Isabelle Aerts</name>
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<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<name sortKey="Bouffet, Eric" sort="Bouffet, Eric" uniqKey="Bouffet E" first="Eric" last="Bouffet">Eric Bouffet</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<name sortKey="Bailey, Simon" sort="Bailey, Simon" uniqKey="Bailey S" first="Simon" last="Bailey">Simon Bailey</name>
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<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<name sortKey="Leary, Sarah" sort="Leary, Sarah" uniqKey="Leary S" first="Sarah" last="Leary">Sarah Leary</name>
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<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
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<name sortKey="Macdonald, Tobey J" sort="Macdonald, Tobey J" uniqKey="Macdonald T" first="Tobey J" last="Macdonald">Tobey J. Macdonald</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
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<name sortKey="Mechinaud, Francoise" sort="Mechinaud, Francoise" uniqKey="Mechinaud F" first="Francoise" last="Mechinaud">Francoise Mechinaud</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Cohen, Kenneth J" sort="Cohen, Kenneth J" uniqKey="Cohen K" first="Kenneth J" last="Cohen">Kenneth J. Cohen</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Riccardi, Riccardo" sort="Riccardi, Riccardo" uniqKey="Riccardi R" first="Riccardo" last="Riccardi">Riccardo Riccardi</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Mason, Warren" sort="Mason, Warren" uniqKey="Mason W" first="Warren" last="Mason">Warren Mason</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Hargrave, Darren" sort="Hargrave, Darren" uniqKey="Hargrave D" first="Darren" last="Hargrave">Darren Hargrave</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kalambakas, Stacey" sort="Kalambakas, Stacey" uniqKey="Kalambakas S" first="Stacey" last="Kalambakas">Stacey Kalambakas</name>
</author>
<author>
<name sortKey="Deshpande, Priya" sort="Deshpande, Priya" uniqKey="Deshpande P" first="Priya" last="Deshpande">Priya Deshpande</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Tai, Feng" sort="Tai, Feng" uniqKey="Tai F" first="Feng" last="Tai">Feng Tai</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Hurh, Eunju" sort="Hurh, Eunju" uniqKey="Hurh E" first="Eunju" last="Hurh">Eunju Hurh</name>
</author>
<author>
<name sortKey="Geoerger, Birgit" sort="Geoerger, Birgit" uniqKey="Geoerger B" first="Birgit" last="Geoerger">Birgit Geoerger</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
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<title xml:lang="en">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.</title>
<author>
<name sortKey="Kieran, Mark W" sort="Kieran, Mark W" uniqKey="Kieran M" first="Mark W" last="Kieran">Mark W. Kieran</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Chisholm, Julia" sort="Chisholm, Julia" uniqKey="Chisholm J" first="Julia" last="Chisholm">Julia Chisholm</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Casanova, Michela" sort="Casanova, Michela" uniqKey="Casanova M" first="Michela" last="Casanova">Michela Casanova</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Brandes, Alba A" sort="Brandes, Alba A" uniqKey="Brandes A" first="Alba A" last="Brandes">Alba A. Brandes</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Aerts, Isabelle" sort="Aerts, Isabelle" uniqKey="Aerts I" first="Isabelle" last="Aerts">Isabelle Aerts</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Bouffet, Eric" sort="Bouffet, Eric" uniqKey="Bouffet E" first="Eric" last="Bouffet">Eric Bouffet</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Bailey, Simon" sort="Bailey, Simon" uniqKey="Bailey S" first="Simon" last="Bailey">Simon Bailey</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Leary, Sarah" sort="Leary, Sarah" uniqKey="Leary S" first="Sarah" last="Leary">Sarah Leary</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Macdonald, Tobey J" sort="Macdonald, Tobey J" uniqKey="Macdonald T" first="Tobey J" last="Macdonald">Tobey J. Macdonald</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Mechinaud, Francoise" sort="Mechinaud, Francoise" uniqKey="Mechinaud F" first="Francoise" last="Mechinaud">Francoise Mechinaud</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Cohen, Kenneth J" sort="Cohen, Kenneth J" uniqKey="Cohen K" first="Kenneth J" last="Cohen">Kenneth J. Cohen</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Riccardi, Riccardo" sort="Riccardi, Riccardo" uniqKey="Riccardi R" first="Riccardo" last="Riccardi">Riccardo Riccardi</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Mason, Warren" sort="Mason, Warren" uniqKey="Mason W" first="Warren" last="Mason">Warren Mason</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Hargrave, Darren" sort="Hargrave, Darren" uniqKey="Hargrave D" first="Darren" last="Hargrave">Darren Hargrave</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Kalambakas, Stacey" sort="Kalambakas, Stacey" uniqKey="Kalambakas S" first="Stacey" last="Kalambakas">Stacey Kalambakas</name>
</author>
<author>
<name sortKey="Deshpande, Priya" sort="Deshpande, Priya" uniqKey="Deshpande P" first="Priya" last="Deshpande">Priya Deshpande</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Tai, Feng" sort="Tai, Feng" uniqKey="Tai F" first="Feng" last="Tai">Feng Tai</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Hurh, Eunju" sort="Hurh, Eunju" uniqKey="Hurh E" first="Eunju" last="Hurh">Eunju Hurh</name>
</author>
<author>
<name sortKey="Geoerger, Birgit" sort="Geoerger, Birgit" uniqKey="Geoerger B" first="Birgit" last="Geoerger">Birgit Geoerger</name>
<affiliation>
<nlm:affiliation>Pediatric 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.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Neuro-oncology</title>
<idno type="eISSN">1523-5866</idno>
<imprint>
<date when="2017" type="published">2017</date>
</imprint>
</series>
</biblStruct>
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<textClass></textClass>
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<front>
<div type="abstract" xml:lang="en">Sonidegib (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.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="In-Process" Owner="NLM">
<PMID Version="1">28605510</PMID>
<DateCreated>
<Year>2017</Year>
<Month>06</Month>
<Day>12</Day>
</DateCreated>
<DateRevised>
<Year>2017</Year>
<Month>10</Month>
<Day>23</Day>
</DateRevised>
<Article PubModel="Print">
<Journal>
<ISSN IssnType="Electronic">1523-5866</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>19</Volume>
<Issue>11</Issue>
<PubDate>
<Year>2017</Year>
<Month>Oct</Month>
<Day>19</Day>
</PubDate>
</JournalIssue>
<Title>Neuro-oncology</Title>
<ISOAbbreviation>Neuro-oncology</ISOAbbreviation>
</Journal>
<ArticleTitle>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.</ArticleTitle>
<Pagination>
<MedlinePgn>1542-1552</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1093/neuonc/nox109</ELocationID>
<Abstract>
<AbstractText Label="Background" NlmCategory="UNASSIGNED">Sonidegib (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.</AbstractText>
<AbstractText Label="Methods" NlmCategory="UNASSIGNED">Pediatric 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.</AbstractText>
<AbstractText Label="Results" NlmCategory="UNASSIGNED">Sixteen 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.</AbstractText>
<AbstractText Label="Conclusions" NlmCategory="UNASSIGNED">Sonidegib 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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Kieran</LastName>
<ForeName>Mark W</ForeName>
<Initials>MW</Initials>
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