RecruitingPhase 1ACTRN12623000104651

Phase I Trial of Deflexifol for Refractory or Recurrent Paediatric Central Nervous System (CNS) Tumours

Phase I Trial of the Safety and Efficacy of Deflexifol for Refractory or Recurrent Paediatric Central Nervous System (CNS) Tumours

Sponsor

Australian and New Zealand Children’s Haematology and Oncology Group (ANZCHOG)

Enrollment

24 participants

Start Date

Aug 29, 2023

Study Type

Interventional

Conditions

Central Nervous System Tumour Diffuse Intrinsic Pontine Glioma Ependymoma Diffuse Midline Glioma

Summary

This is a multicentre Phase I clinical trial to establish if Deflexifol is safe and effective in children, adolescents and young adults with recurrent or refractory brain tumours. Who is it for? Participants may be eligible for this study if they are older than 12 months and up to 21 years old and have a recurrent or refractory brain tumour; or newly diagnosed diffuse intrinsic pontine glioma (DIPG) or diffuse midline glioma (DMG) participants after completion of radiotherapy. Study details Participants will receive Deflexifol every 2 weeks for up to approximately one year, if there is ongoing clinical benefit. Deflexifol will be administered via an injection over 3-5 minutes (bolus), followed by a continuous intravenous infusion over 46 hours. Pharmacokinetics will be measured during the first 4 weeks and safety will be assessed throughout the course of treatment and during follow up visits. Participants will have physical examinations, blood tests, urine tests, echocardiogram, electrocardiogram (ECG) and MRI scans. This study will test the safety and effectiveness of this new drug in children and adolescents in cases where treatment options are limited.

Eligibility

Sex: Both males and femalesMin Age: 12 MonthssMax Age: 21 Yearss

Plain Language Summary

Simplified for easier understanding

Brain tumours in children and young people are among the most difficult cancers to treat. When a tumour comes back (recurs) or stops responding to treatment (becomes refractory), options are extremely limited. Deflexifol is a new formulation of the chemotherapy drug 5-fluorouracil that has been designed to work differently from existing treatments and may be active against brain tumours in this setting. This Phase I study is the first step in testing Deflexifol specifically in children, adolescents, and young adults. The primary goal is to establish that it is safe and to find the right dose. Participants will receive Deflexifol every two weeks via an intravenous infusion — a short bolus injection followed by a 46-hour continuous infusion — for up to approximately one year if the treatment appears to be helping. Careful monitoring will include blood tests, MRI scans, heart tests, and quality of life assessments throughout. You may be eligible if you are older than 12 months and up to 21 years of age and have a recurrent or treatment-resistant brain tumour, or if you have been newly diagnosed with diffuse intrinsic pontine glioma (DIPG) or diffuse midline glioma (DMG) and have completed radiotherapy. This is a multicentre study for a patient population where new treatments are urgently needed.

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Interventions

This is a phase I multicentre study evaluating the use of Deflexifol in the treatment of children and young adults (greater than 12 months and less than or equal to 21 years) with refractory/recurrent central nervous system (CNS) tumours. Deflexifol is a novel bioequivalent formulation of 5-fluorouracil and leucovorin that has been shown to be safe and effective in adults with advanced/ refractory solid tumours. Phase I (or Part A) will be open to any participant with refractory or recurrent CNS tumours or diffuse intrinsic pontine glioma (DIPG)/diffuse midline glioma (DMG) after upfront radiotherapy. It will evaluate the safety profile and recommended phase II dose (RP2D) of deflexifol in participants with refractory/recurrent CNS tumours, or participants with newly diagnosed DIPG/DMG who have completed radiotherapy. Deflexifol will be administered on Days 1 and 15 of a 28 day cycle. Deflexifol will initially be administered via an injection over 3-5 minutes (bolus), followed by a continuous intravenous infusion over 46 hours (infusional). Depending on the treating doctor and each participant’s condition, the treating doctor may elect to continue the treatment at home or in hospital. The following four dose levels will be tested, starting dose is Dose level 0: Dose level -2: Deflexifol bolus dose of 525mg/m2 and infusional dose of 2400mg/m2 over 46 hours Dose level -1: Deflexifol bolus dose of 525mg/m2 and infusional dose of 3000mg/m2 over 46 hours Dose level 0: Deflexifol bolus dose of 525mg/m2 and infusional dose of 3400mg/m2 over 46 hours Dose level +1: Deflexifol bolus dose of 525mg/m2 and infusional dose of 3800mg/ m2 over 46 hours Each participant will be assigned a dose level at the start of treatment and will remain at the dose for the duration of the study. Participants may receive a minimum of 1 dose of study drug and a maximum of one year of study drug, as long as the participant is able to tolerate treatment. Dosing will follow a dose de-escalation or escalation scheme which will be determined by biological effect of the drug (measured in participant blood samples) and levels of toxicity (measured by dose limiting toxicity and adverse event observed). A recommended phase 2 dose (RP2D) will be determined in this Phase I study.