Roadmap for the next generation of Children's Oncology Group rhabdomyosarcoma trials

Jonathan L Metts^{1

2}, Jamie M Aye³, Jacquelyn N Crane^{4

5}, Sapna Oberoi^{6

7}, Frank M Balis⁴, Smita Bhatia⁸, Kira Bona^{9

10}, Bruce Carleton¹¹, Roshni Dasgupta¹², Filemon S Dela Cruz¹³, Katie A Greenzang^{9

10}, Jonathan L Kaufman^{14

15}, Corinne M Linardic^{16

17}, Susan K Parsons¹⁸, Mark Robertson-Tessi¹⁹, Erin R Rudzinski²⁰, Alice Soragni^{21

22}, Elizabeth Stewart²³, Brenda J Weigel²⁴, Suzanne L Wolden²⁵, Aaron R Weiss²⁶, Rajkumar Venkatramani²⁷, Christine M Heske²⁸

Affiliations

¹ Sarcoma Department, Moffitt Cancer Center, Tampa, Florida, USA.
² Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Florida, USA.
³ Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁵ Department of Pediatrics, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Department of Pediatric Hematology/Oncology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada.
⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
⁸ Institute for Cancer Outcomes and Survivorship, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁹ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
¹⁰ Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
¹¹ Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
¹² Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
¹³ Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
¹⁴ Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, USA.
¹⁵ Patient Advocacy Committee, Children's Oncology Group, Monrovia, California, USA.
¹⁶ Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁷ Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁸ Institute for Clinical Research and Health Policy Studies and Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts, USA.
¹⁹ Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
²⁰ Department of Laboratory Medicine and Pathology, Seattle Children's Hospital and University of Washington Medical Center, Seattle, Washington, USA.
²¹ Department of Orthopedic Surgery, University of California Los Angeles, Los Angeles, CA, USA.
²² Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA.
²³ Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
²⁴ Division of Pediatric Hematology Oncology, University of Minnesota, Minneapolis, Minnesota, USA.
²⁵ Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
²⁶ Department of Pediatrics, Maine Medical Center, Portland, Maine, USA.
²⁷ Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
²⁸ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.

PMID: 38941509
PMCID: PMC11511643
DOI: 10.1002/cncr.35457

Roadmap for the next generation of Children's Oncology Group rhabdomyosarcoma trials

Jonathan L Metts et al. Cancer. 2024.

. 2024 Nov 15;130(22):3785-3796.

doi: 10.1002/cncr.35457. Epub 2024 Jun 28.

Authors

Affiliations

¹ Sarcoma Department, Moffitt Cancer Center, Tampa, Florida, USA.
² Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Florida, USA.
³ Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁵ Department of Pediatrics, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁶ Department of Pediatric Hematology/Oncology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada.
⁷ Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
⁸ Institute for Cancer Outcomes and Survivorship, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁹ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
¹⁰ Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
¹¹ Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
¹² Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
¹³ Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
¹⁴ Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, USA.
¹⁵ Patient Advocacy Committee, Children's Oncology Group, Monrovia, California, USA.
¹⁶ Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁷ Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA.
¹⁸ Institute for Clinical Research and Health Policy Studies and Division of Hematology/Oncology, Tufts Medical Center, Boston, Massachusetts, USA.
¹⁹ Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
²⁰ Department of Laboratory Medicine and Pathology, Seattle Children's Hospital and University of Washington Medical Center, Seattle, Washington, USA.
²¹ Department of Orthopedic Surgery, University of California Los Angeles, Los Angeles, CA, USA.
²² Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA.
²³ Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
²⁴ Division of Pediatric Hematology Oncology, University of Minnesota, Minneapolis, Minnesota, USA.
²⁵ Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
²⁶ Department of Pediatrics, Maine Medical Center, Portland, Maine, USA.
²⁷ Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
²⁸ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.

PMID: 38941509
PMCID: PMC11511643
DOI: 10.1002/cncr.35457

Abstract

Clinical trials conducted by the Intergroup Rhabdomyosarcoma (RMS) Study Group and the Children's Oncology Group have been pivotal to establishing current standards for diagnosis and therapy for RMS. Recent advancements in understanding the biology and clinical behavior of RMS have led to more nuanced approaches to diagnosis, risk stratification, and treatment. The complexities introduced by these advancements, coupled with the rarity of RMS, pose challenges to conducting large-scale phase 3 clinical trials to evaluate new treatment strategies for RMS. Given these challenges, systematic planning of future clinical trials in RMS is paramount to address pertinent questions regarding the therapeutic efficacy of drugs, biomarkers of response, treatment-related toxicity, and patient quality of life. Herein, the authors outline the proposed strategic approach of the Children's Oncology Group Soft Tissue Sarcoma Committee to the next generation of RMS clinical trials, focusing on five themes: improved novel agent identification and preclinical to clinical translation, more efficient trial development and implementation, expanded opportunities for knowledge generation during trials, therapeutic toxicity reduction and quality of life, and patient engagement.

Keywords: clinical trials; novel agents; pediatric; quality of life; rhabdomyosarcoma.

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Conflict of interest statement

DISCLOSURES/CONFLICTS OF INTEREST: AS is a founder and owner of Icona BioDx. The remaining authors have no conflicts of interest related to this work.

Figures

**Figure 1:**
Proposed strategic approach for the development and implementation of the next generation of Children’s Oncology Group rhabdomyosarcoma trials. Abbreviations: DVL: developmental therapeutics, PD: pharmacodynamics, PGx: pharmacogenomics, PIVOT: Pediatric Preclinical In Vivo Testing Progam, PK: pharmacokinetics, PROs: patient-reported outcomes, PROXC: Pediatric Research Oncology Xenografting Consortium. Figure created with BioRender.com

See this image and copyright information in PMC

References

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Roadmap for the next generation of Children's Oncology Group rhabdomyosarcoma trials

Affiliations

Roadmap for the next generation of Children's Oncology Group rhabdomyosarcoma trials

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical