1. Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies
- Author
-
Mignon L. Loh, Thalia A. Farazi, Daniel A. Morgenstern, C. Michel Zwaan, Kelly C. Goldsmith, Jean-Pierre Bourquin, Maria Verdugo, Yeshwant D. Sanzgiri, Josef Vormoor, David Hoffman, Mohamad Shebley, Betty Prine, Megan McNamee, Andrew E. Place, Jeremy A. Ross, Lia Gore, Ying Zhou, Su Young Kim, L. Leanne Lash-Fleming, University of Zurich, Place, Andrew E, and Pediatrics
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,medicine.medical_treatment ,Antineoplastic Agents ,610 Medicine & health ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Clinical Protocols ,Drug Development ,SDG 3 - Good Health and Well-being ,Refractory ,Recurrence ,Neoplasms ,Internal medicine ,medicine ,Humans ,1306 Cancer Research ,Sulfonamides ,Chemotherapy ,business.industry ,Venetoclax ,Age Factors ,General Medicine ,Bridged Bicyclo Compounds, Heterocyclic ,medicine.disease ,Pediatric cancer ,Phase i study ,Treatment Outcome ,030104 developmental biology ,Drug development ,chemistry ,Drug Resistance, Neoplasm ,Research Design ,10036 Medical Clinic ,Child, Preschool ,030220 oncology & carcinogenesis ,Relapsed refractory ,2730 Oncology ,business ,Biomarkers - Abstract
Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).
- Published
- 2018
- Full Text
- View/download PDF