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

Author:

Mueller Sabine12ORCID,Fangusaro Jason3,Thomas Arzu Onar4,Jacques Thomas S5,Bandopadhayay Pratiti678ORCID,de Blank Peter9ORCID,Packer Roger J101112,Fouladi Maryam13ORCID,van Meeteren Antoinette Schouten14,Jones David15,Perry Arie16,Nakano Yoshiko17,Hargrave Darren18,Riedl David1920,Robinson Nathan J2122,Partanen Marita23,Fisher Michael J24,Witt Olaf25

Affiliation:

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

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Neurology (clinical),Oncology

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