Considerations for Clinical Trial Design in Relapsed and Refractory Osteosarcoma: An FDA Symposium.

Journal: Clinical cancer research : an official journal of the American Association for Cancer Research

This publication is a concise report from an FDA Oncology Center of Excellence mini‑symposium held in May 2023, focused on clinical trial design for relapsed and refractory osteosarcoma in children and adolescents.

Key points:

  • Clinical context:
    • Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, peaking around puberty.
    • Around 10%–20% present with metastatic disease, most often in the lungs.
    • With current multimodality therapy, 5‑year overall survival is ~70% for localized disease but only ~30% for metastatic or recurrent disease in the pediatric population.
    • There is no standard of care or approved therapy for relapsed/refractory disease.
  • Barriers to progress:
    • Complex biology and the rarity of osteosarcoma limit drug development.
    • Conventional clinical trial endpoints, especially objective response rate, are unreliable indicators of meaningful drug activity in this setting.
    • Trial design and implementation in this rare population are logistically and methodologically challenging.
  • Symposium focus:
    • Brought together patient advocates, FDA regulators, and pediatric sarcoma experts to review current obstacles and discuss how to improve trial design.
    • Emphasized the need for endpoints and study designs that better capture clinical benefit and are feasible in small, heterogeneous populations.
  • Main conclusion:
    • Moving the field forward will require deliberate, sustained collaboration among all stakeholders—patients, regulators, and investigators—to create trials that are patient-acceptable and capable of generating evidence robust enough to support future marketing applications.
    • The article summarizes the core themes and outlines future directions discussed at the meeting, aiming to guide more effective trial strategies in relapsed/refractory osteosarcoma.

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