Consensus framework for conducting phase I/II clinical trials for children, adolescents, and young adults with pediatric low-grade glioma: Guidelines established by the International Pediatric Low-Grade Glioma Coalition Clinical Trial Working Group

Sabine Mueller; Jason Fangusaro; Arzu Onar Thomas; Thomas S Jacques; Pratiti Bandopadhayay; Peter de Blank; Roger J Packer; Maryam Fouladi; Antoinette Schouten van Meeteren; David Jones; Arie Perry; Yoshiko Nakano; Darren Hargrave; David Riedl; Nathan J Robison; Marita Partanen; Michael J Fisher; Olaf Witt

doi:10.1093/neuonc/noad227

Consensus framework for conducting phase I/II clinical trials for children, adolescents, and young adults with pediatric low-grade glioma: Guidelines established by the International Pediatric Low-Grade Glioma Coalition Clinical Trial Working Group

Neuro Oncol. 2024 Mar 4;26(3):407-416. doi: 10.1093/neuonc/noad227.

Authors

Sabine Mueller^{1

2}, Jason Fangusaro³, Arzu Onar Thomas⁴, Thomas S Jacques⁵, Pratiti Bandopadhayay^{6

7

8}, Peter de Blank⁹, Roger J Packer^{10

11

12}, Maryam Fouladi¹³, Antoinette Schouten van Meeteren¹⁴, David Jones¹⁵, Arie Perry¹⁶, Yoshiko Nakano¹⁷, Darren Hargrave¹⁸, David Riedl^{19

20}, Nathan J Robison^{21

22}, Marita Partanen²³, Michael J Fisher²⁴, Olaf Witt²⁵

Affiliations

¹ Department of Neurology, Neurological Surgery and Pediatrics, University of California, San Francisco, San Francisco, California, USA.
² Department of Pediatrics, University Children's Hospital, University of Zurich, Zürich, Switzerland.
³ Department of Hematology and Oncology, Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA.
⁴ Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁵ UCL Great Ormond Street Institute of Child Health and Histopathology Department, Developmental Biology and Cancer Programme, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
⁶ Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
⁷ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁹ Department of Pediatrics, University of Cincinnati Medical Center and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁰ Brain Tumor Institute, Washington DC, USA.
¹¹ Gilbert Family Neurofibromatosis Institute, Washington DC, USA.
¹² Center for Neuroscience and Behavioral Medicine, Children's National Hospital, Washington, District of Columbia, USA.
¹³ Pediatric Brain Tumor Program, Division of Hematology, Oncology, and Bone Marrow Transplant, Nationwide Children's Hospital, Columbus, Ohio, USA.
¹⁴ Princess Màxima Center for Pediatric Oncology, Department of Neuro-oncology, Utrecht, The Netherlands.
¹⁵ Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
¹⁶ Departments of Pathology and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
¹⁷ Division of Haematology/Oncology, Hospital for Sick Children, Toronto, Canada.
¹⁸ Department of Paediatric Oncology, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
¹⁹ Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, University Hospital of Psychiatry II, Medical University of Innsbruck, Innsbruck, Austria.
²⁰ Ludwig Boltzmann Institute for Rehabilitation Research, Vienna, Austria.
²¹ Division of Hematology and Oncology, Children's Hospital Los Angeles, Los Angeles, California, USA.
²² Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
²³ Department of Research, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
²⁴ Division of Oncology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁵ Hopp Children's Cancer Center (KiTZ), National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ) and University Hospital, Heidelberg, Germany.

PMID: 38146999
PMCID: PMC10912006 (available on 2024-12-26)
DOI: 10.1093/neuonc/noad227

Abstract

Within the last few decades, we have witnessed tremendous advancements in the study of pediatric low-grade gliomas (pLGG), leading to a much-improved understanding of their molecular underpinnings. Consequently, we have achieved successful milestones in developing and implementing targeted therapeutic agents for treating these tumors. However, the community continues to face many unknowns when it comes to the most effective clinical implementation of these novel targeted inhibitors or combinations thereof. Questions encompassing optimal dosing strategies, treatment duration, methods for assessing clinical efficacy, and the identification of predictive biomarkers remain unresolved. Here, we offer the consensus of the international pLGG coalition (iPLGGc) clinical trial working group on these important topics and comment on clinical trial design and endpoint rationale. Throughout, we seek to standardize the global approach to early clinical trials (phase I and II) for pLGG, leading to more consistently interpretable results as well as enhancing the pace of novel therapy development and encouraging an increased focus on functional endpoints as well and quality of life for children faced with this disease.

Keywords: Consensus recommendation; Early phase clinical trial; Low grade glioma.

MeSH terms

Adolescent
Antineoplastic Agents* / therapeutic use
Brain Neoplasms* / drug therapy
Brain Neoplasms* / pathology
Child
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Consensus
Glioma* / drug therapy
Glioma* / pathology
Humans
Practice Guidelines as Topic
Quality of Life
Treatment Outcome
Young Adult

Substances

Antineoplastic Agents