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)


Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
10 2021
Historique:
received: 26 05 2021
revised: 27 07 2021
accepted: 03 08 2021
pubmed: 26 9 2021
medline: 30 10 2021
entrez: 25 9 2021
Statut: ppublish

Résumé

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). 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 progression-free 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. In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m The lenvatinib RP2D was 14 mg/m

Sections du 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 progression-free 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
CONCLUSIONS
The lenvatinib RP2D was 14 mg/m

Identifiants

pubmed: 34562750
pii: S2059-7029(21)00211-8
doi: 10.1016/j.esmoop.2021.100250
pmc: PMC8477142
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Iodine Radioisotopes 0
Phenylurea Compounds 0
Quinolines 0
lenvatinib EE083865G2

Banques de données

ClinicalTrials.gov
['NCT04447755', 'NCT02432274']

Types de publication

Clinical Trial, Phase I Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

100250

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure SGM: personal fees from Loxo Oncology, Bayer, and EUSA Pharma, outside the submitted work. FL: consultant or advisory role for Novartis, Amgen, Bellicum Pharmaceuticals, and Pfizer; honoraria for speaking at symposia from Amgen, Novartis, bluebird bio, Miltenyi, Bellicum Pharmaceuticals, and Jazz Pharmaceuticals. FB: consultant or advisory role for Bayer, Amgen, Roche, Sanofi, and EUSA Pharma; honoraria for speaking at symposia from Amgen and Jazz Pharmaceuticals; support for attending symposia from Takeda, EUSA Pharma, Shire, and Jazz Pharmaceuticals. CR: consultant or advisory role for Amgen, Bristol Myers Squibb (BMS), Celgene, Genentech, Novartis, Pfizer, and Roche. ACN: personal fees from Bayer and EUSA Pharma, outside of the submitted work. AL: nonfinancial support and ‘other’ from PharmaMar; grants and nonfinancial support from Takeda, during the conduct of the study. SJS: consultant or advisory role for Lilly outside the submitted work. CO: employee of Eisai Ltd. CH: employee of Eisai Inc. LD: employee of Eisai Inc. MC: advisory roles for AstraZeneca, Bayer, BMS, Eisai, Lilly, and Roche outside the submitted work. All other authors have declared no conflicts of interest.

Auteurs

N Gaspar (N)

Department of Childhood and Adolescent Oncology, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: nathalie.gaspar@gustaveroussy.fr.

Q Campbell-Hewson (Q)

The Great North Children's Hospital, Royal Victoria Infirmary, Newcastle Upon Tyne, UK.

S Gallego Melcon (S)

Pediatric Oncology and Hematology Service, University Hospital Vall d'Hebron, Barcelona, Spain.

F Locatelli (F)

Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, University of Rome, Rome, Italy.

R Venkatramani (R)

Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, USA.

S Hecker-Nolting (S)

Department of Pediatric Oncology, Hematology, Immunology, Klinikum Stuttgart - Olgahospital, Stuttgart, Germany.

M Gambart (M)

Pediatric Hemato-Oncology Unit, CHU Toulouse - Hôpital des Enfants, URCP, Toulouse, France.

F Bautista (F)

Paediatric Haematology-Oncology Department, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.

E Thebaud (E)

Pediatric Oncology-Hematology and Immunology Department, CHU Nantes - Hôpital Mère-Enfant, Nantes, France.

I Aerts (I)

SIREDO Oncology Center, Institut Curie, PSL Research University, Paris, France.

B Morland (B)

Department of Paediatric Hematology/Oncology, Birmingham Children's Hospital, Birmingham, UK.

C Rossig (C)

Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.

A Canete Nieto (A)

Children's Oncology Unit, Pediatric Service, Hospital Universitario y Politecnico La Fe, Valencia, Spain.

A Longhi (A)

Chemotherapy Service, Istituto Ortopedico Rizzoli IRCCS, Bologna, Italy.

C Lervat (C)

Pediatric and AYA Oncology Unit, Centre Oscar Lambret Lille, Lille, France.

N Entz-Werle (N)

Pediatric Onco-Hematology Unit, Chu Strasbourg-Hôpital Hautepierre, Strasbourg, France.

S J Strauss (SJ)

Clinical Research Facility, University College London Hospitals NHS Trust, London, UK.

P Marec-Berard (P)

Institute of Pediatric Hematology and Oncology, Centre Léon Bérard, Lyon, France.

C E Okpara (CE)

Clinical Research, Oncology Business Group, Eisai Ltd., Hatfield, UK.

C He (C)

Biostatistics, Oncology Business Group, Eisai Inc., Woodcliff Lake, USA.

L Dutta (L)

Clinical Research, Oncology Business Group, Eisai Inc., Woodcliff Lake, USA.

M Casanova (M)

Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

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Classifications MeSH