CTP-02. A Phase 1 trial of Deflexifol™ in pediatric patients with relapsed or refractory brain tumors
Year: 2025
Type: conference-abstract
Abstract: BACKGROUND Deflexifol is a novel combination of 5-fluorouracil (5-FU) and leucovorin, allowing for co-delivery in one infusion. 5-FU has documented activity in pediatric ependymoma. It is hypothesized that this novel formulation will enhance efficacy and reduce toxicity, enabling higher active doses within the brain. We report results of a first-in-child Phase 1 trial of Deflexifol in children with relapsed or refractory brain tumors including ependymoma. METHODS Children (aged 1-21 years) with relapsed or refractory brain tumors were eligible for Phase 1 enrolment, using a rolling 6 design. Intravenous Deflexifol was administered on Days 1-3 and Days 15-17 of a 28-day cycle, as a bolus followed by a 46-hour infusion. The starting dose (Dose level 0) was a 525mg/m2 bolus (of delivered 5-FU) and 3400mg/m2 infusion, with pre-defined levels for dose escalation/de-escalation. The maximum tolerated dose (MTD) was determined based on cycle 1 dose-limiting toxicity (DLT) (Common Terminology Criteria for Adverse Events, v5.0). Pharmacokinetic samples were collected. RESULTS Nine participants (aged 4-14 years), with ependymoma (n=6), DMG (n=2), ETMR (n=1) were enrolled. At the starting dose, two of three participants experienced DLTs of Grade 3 oral mucositis and Grade 4 neutropenia. Six participants were enrolled at Dose level -1 (525mg/m2 bolus and 3000mg/m2 infusion), with one DLT of Grade 4 neutropenia. Grade 3 and 4 non-DLTs included: neutropenia (14 occurrences), leucopenia (4), febrile neutropenia (3), oral mucositis (2) and palmar-plantar erythrodysesthesia syndrome (2). No participants discontinued treatment due to toxicity. Pharmacokinetic analysis is ongoing and will be presented. CONCLUSIONS The pediatric MTD and Recommended Phase 2 Dose for Deflexifol are 525mg/m2 bolus and 3000mg/m2 infusion, equivalent to 88% of the adult MTD. This study has demonstrated that Deflexifol is well tolerated in children. A Phase 2 expansion cohort is planned to evaluate the activity of Deflexifol in children with ependymoma.
Source: Neuro-Oncology
Institutions: UNSW Sydney, Sydney Children's Hospital, The Kids Research Institute Australia, Princess Margaret Hospital for Children, Perth Children's Hospital, The University of Queensland, Children's Health Queensland Hospital and Health Service, Monash Medical Centre, Monash Children’s Hospital, Monash Health, Women's and Children's Hospital, South Australian Health and Medical Research Institute, The University of Adelaide, Royal Children's Hospital, Murdoch Children's Research Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416140953
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