ID #636 Phase I/II trial of axitinib and etoposide in children with refractory or relapsed medulloblastoma or ependymoma: MEPENDAX report
Caroline Donzé, Gabriel Revon-Rivière, Pierre Leblond, Sylvie Abed, Nicolas André, Franck Bourdeaut, Natacha Entz-Werle, Stéphane Ducassou, Roch GiorgiAbstract
Background
Medulloblastoma and ependymoma remain challenging to treat after relapse or in refractory cases [1]. This phase I/II trial evaluated the combination of axitinib, an oral pan-VEGF receptor inhibitor, with etoposide in pediatric patients with refractory or relapsed medulloblastoma or ependymoma, based on the results of a previous preliminary study [2]. Primary objectives were to: 1) determine the recommended phase II dose (RP2D) of axitinib when combined with etoposide; 2) characterize the safety profile of this combination; and 3) assess efficacy by comparing progression-free survival (PFS) and overall survival (OS) against historical controls from prior trials.
Methods
Patients received axitinib twice daily and oral etoposide at 25 mg/m²/day once daily in 28-day cycles for up to 13 cycles. Axitinib dose escalation followed a standard 3 + 3 design across three dose levels: 1.6, 2.0, and 2.4 mg/m²/day (levels 1-3). Toxicities were monitored and graded according to CTCAE v5.0. Tumor response was assessed by MRI every two cycles using RANO criteria. We present herein the result of phase I dose levels one and two.
Results
Overall, 14 patients (median age 168 months [range: 72-264]) were enrolled across 7 centers in the phase I study. The RP2D of axitinib combined with etoposide will be established at 2.4 mg/m²/day. The regimen was well-tolerated, with treatment discontinuation due to toxicity occurring in only 0% (n = 0) of patients. Most common toxicities included neutropenia (n = 10, 17.5%) and nausea/vomiting (n = 6, 10.5%). Dose-limiting toxicities (DLTs) occurred in 0 patients.
Conclusion
The combination of axitinib and etoposide currently demonstrated acceptable tolerability in children with refractory or relapsed medulloblastoma or ependymoma. The RP2D will be established, and ongoing phase II enrollment will provide definitive efficacy data.
1. Udaka YT, Packer RJ. Pediatric Brain Tumors. Neurol Clin. 2018 Aug;36(3):533-556. doi: 10.1016/j.ncl.2018.04.009. PMID: 30072070.
2. Donzé C, Revon-Rivière G, Pondrom M, Verschuur A, Leblond P, André N. Retrospective experience of children with relapsed brain tumors treated with oral combination of axitinib and metronomic etoposide. Pediatr Blood Cancer. 2024 Aug;71(8):e31076. doi: 10.1002/pbc.31076. Epub 2024 May 22. PMID: 38778441.