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Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials

Journal Article · · Clinical Pharmacology and Therapeutics
DOI:https://doi.org/10.1002/cpt.2467· OSTI ID:1981403
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  1. Center for Drug Evaluation and Research, Silver Spring, MD (United States)
  2. U.S. Food and Drug Administration (FDA), Silver Spring, MD (United States)
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Our research supported the dose selection recommendations for adolescents in the US Food and Drug Administration (FDA) Guidance on Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. The FDA Guidance states that for drugs administered as a flat dose in adults and data showing no clinically meaningful effect of body size on drug exposure and toxicity in adults, a minimum body weight threshold may need to be defined to prevent adolescents who have a lower body weight from exceeding adult exposures. Our review of adult population pharmacokinetic analyses of new molecular entities approved for oncology between January 2015 and March 2021 suggested that 40 kg (the approximate median body weight of a 12-year-old) is generally the lower end of the body weight range that has no clinically relevant effect on drug pharmacokinetics or safety. In conclusion, the minimum body weight threshold and selection of an appropriate dose for adolescents in relevant adult oncology clinical trials should ultimately be determined based on available data on pharmacokinetics or pharmacodynamics of the investigational drug with consideration of body size effect on drug exposure, toxicity, and efficacy data (if available), the therapeutic index of the drug, and dose- and exposure-response relationships in adults.

Research Organization:
Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC); U.S. Food and Drug Administration (FDA)
Grant/Contract Number:
SC0014664
OSTI ID:
1981403
Alternate ID(s):
OSTI ID: 1832047
Journal Information:
Clinical Pharmacology and Therapeutics, Journal Name: Clinical Pharmacology and Therapeutics Journal Issue: 4 Vol. 111; ISSN 0009-9236
Publisher:
American Society for Clinical Pharmacology & Therapeutics - WileyCopyright Statement
Country of Publication:
United States
Language:
English

References (12)

Adolescent Dosing and Labeling Since the Food and Drug Administration Amendments Act of 2007 journal October 2013
Allometry Is a Reasonable Choice in Pediatric Drug Development: Journal of Clinical Pharmacology journal November 2016
The Integration of Allometry and Virtual Populations to Predict Clearance and Clearance Variability in Pediatric Populations over the Age of 6 Years journal April 2013
The distinctive biology of cancer in adolescents and young adults journal April 2008
Reevaluating Eligibility Criteria — Balancing Patient Protection and Participation in Oncology Trials journal April 2017
Effects of Size and Temperature on Metabolic Rate journal September 2001
Enrolling Adolescents in Disease/Target-Appropriate Adult Oncology Clinical Trials of Investigational Agents journal October 2016
Modernizing Clinical Trial Eligibility: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research Minimum Age Working Group journal November 2017
Treatment Setting, Clinical Trial Enrollment, and Subsequent Outcomes Among Adolescents With Cancer: A Literature Review journal June 2014
Simplification of drug Dosage Calculation by Application of the Surface area Principle journal May 1950
Pediatric Dosing and Body Size in Biotherapeutics journal December 2010
Factors and Mechanisms for Pharmacokinetic Differences between Pediatric Population and Adults journal February 2011

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Related Subjects

60 APPLIED LIFE SCIENCES
Pharmacology & Pharmacy
adolescents in adult oncology clinical trials
dose selection for adolescent patients