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Phase I Study of a Combination of Fluvastatin and Celecoxib in Children with Relapsing/Refractory Low-Grade or High-Grade Glioma (FLUVABREX)

We are very glad to share the recent article reporting the Phase I Study of a Combination of Fluvastatin and Celecoxib in Children with Relapsing/Refractory Low-Grade or High-Grade Glioma (FLUVABREX) by Pierre Leblond ,Emmanuelle Tresch-Bruneel,Alicia Probst ,Nadège Néant,Caroline Solas ,Arthur Sterin,Thomas Boulanger,Isabelle Aerts,Cécile Faure-Conter,Anne-Isabelle Bertozzi ,Pascal Chastagner,Natacha Entz-Werlé, Emilie De Carli,Marie-Cécile Le Deley,Gauthier Bouche and Nicolas André

from the Pediatric Oncology Unit, Oscar Lambret Comprehensive Cancer Center, Lille, the Centre Léon Bérard, Institut d’Hématologie et d’Oncologie Pédiatrique (IHOPe), Lyon, Department of Clinical Research and Innovation, Oscar Lambret Comprehensive Cancer Center, 59037 Lille, the Laboratoire de Pharmacocinétique et Toxicologie, La Timone, AP-HM, 13005 Marseille, The service d’Hématologie et Oncologie Pédiatrique, La Timone, AP-HM, Marseille, France, the Imaging Department, Oscar Lambret Comprehensive Cancer Center, 59037 Lille, the Institut Curie, PSL Research University-Oncology Center SIREDO, Paris, the Pôle de Pédiatrie Unité Hemato-Immuno-Oncologie, Toulouse University Hospital, Toulouse the Service d’Hémato-Oncologie Pédiatrique, Nancy University Hospital, 54500 Vandoeuvre-lès-Nancy, the Pédiatrie Onco-Hématologie—Pédiatrie III, Strasbourg University Hospital, Strasbourg, the Service d’Hémato-Oncologie Pédiatrique, Angers University Hospital, Angers, the Department of Biostatistics, Oscar Lambret Comprehensive Center, 59037 Lille, The Anticancer Fund, 1860 Meise, Belgium, the CRCM INSERM U1068 SMARTc, Aix Marseille University, 13007 Marseille, France and Metronomics Global Health Initiative, 13005 Marseille, France.


Preclinical data support the activity of celecoxib and fluvastatin in high-grade (HGG) and low-grade gliomas (LGG). A phase I trial (NCT02115074) was designed to evaluate the safety of this combination in children with refractory/relapsed HGG and LGG using four dose levels of fluvastatin with a fixed daily dose of celecoxib. A Continual Reassessment Method was used for fluvastatin dose escalation. Dose-limiting toxicities (DLT) were determined on the first treatment cycle. Twenty patients were included. Ten LGG and ten HGG patients received a median of 3.5 treatment cycles. Two DLTs were reported: one grade 3 maculopapular rash (4 mg/kg dose level) and one grade 4 increase of Creatine Phospho-Kinase (6 mg/kg dose level). We identified the dose of 6 mg/kg/day as the recommended phase II dose (RP2D) of fluvastatin with celecoxib. Four patients with LGG continued treatment beyond 12 cycles because of stable disease, including one patient who received 23 treatment cycles. In children with refractory/relapsed glioma, the RP2D of fluvastatin with celecoxib is 6 mg/kg/day. The long-term stable diseases observed in LGG suggest a possible role of the combination in a maintenance setting, given its good tolerance and low cost for children living in low- and middle-income countries.

the full text is freeely avalaible here