Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆ - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue ESMO Open Année : 2021

Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆

Nathalie Gaspar
Quentin Campbell-Hewson
  • Fonction : Auteur
Soledad Gallego Melcon
  • Fonction : Auteur
Franco Locatelli
  • Fonction : Auteur
Rajkumar Venkatramani
  • Fonction : Auteur
Stefanie Hecker-Nolting
  • Fonction : Auteur
Marion Gambart
  • Fonction : Auteur
Francisco José Bautista
  • Fonction : Auteur
Estelle Thebaud
  • Fonction : Auteur
Isabelle Aerts
  • Fonction : Auteur
Bruce J. Morland
  • Fonction : Auteur
C. Rossig
  • Fonction : Auteur
Adela Canete Nieto
  • Fonction : Auteur
Alessandra Longhi
  • Fonction : Auteur
Sandra J. Strauss
  • Fonction : Auteur
Perrine Marec-Berard
  • Fonction : Auteur
Chinyere E. Okpara
  • Fonction : Auteur
Cixin Steven He
  • Fonction : Auteur
Lea Dutta
  • Fonction : Auteur
Michela Casanova
  • Fonction : Auteur

Résumé

Background: We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). Patients and methods: The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progressionfree survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. Results: In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m 2 , three dose-limiting toxicities (hypertension, n ¼ 2; increased alanine aminotransferase, n ¼ 1) were reported, establishing 14 mg/m 2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n ¼ 31], PFS-4 by KaplaneMeier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade !3. Conclusions: The lenvatinib RP2D was 14 mg/m 2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a
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hal-03879123 , version 1 (30-11-2022)

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Nathalie Gaspar, Quentin Campbell-Hewson, Soledad Gallego Melcon, Franco Locatelli, Rajkumar Venkatramani, et al.. Phase I/II study of single-agent lenvatinib in children and adolescents with refractory or relapsed solid malignancies and young adults with osteosarcoma (ITCC-050)☆. ESMO Open, 2021, 6 (5), pp.100250. ⟨10.1016/j.esmoop.2021.100250⟩. ⟨hal-03879123⟩
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