Part 1 (dose escalation, safety, and preliminary efficacy) Part 1 is a non-randomised, single-arm design in 12 participants with recurrent GBM suitable for maximal safe surgical resection. Part 1 will evaluate safety, determine the MTD of irinotecan-ChemoSeed and the RP2D (corresponding to coverage of as much of the resection cavity as possible, up to the MTD) and evaluate efficacy. All Part 1 participants will be administered irinotecan- ChemoSeed concurrent to Standard of Care (SoC) treatment. Part 1 dose- escalation will start at 72 mg of IRN Part 2, in 135 participants with newly diagnosed GBM suitable for maximal safe surgical resection, will assess the efficacy of irinotecan-ChemoSeed. The actual number of irinotecan-ChemoSeeds administered into the resected tumour margin of the tumour cavity after surgical resection will be at the discretion of the neurosurgical consultant up to the MTD, to cover as much of the resection cavity as possible. Participants will be randomised in a 2:1 ratio: * Arm 1: Irinotecan-ChemoSeed +SoC: Irinotecan-Chemoseeds administered into the resection margin following maximal safe surgical resection, with fractionated RT, concomitant and maintenance TMZ (based on Stupp protocol) starting 4 to 6 weeks after surgery per institution standard practice. * Arm 2: SoC treatment only: maximal safe surgical resection with fractionated RT, concomitant and maintenance TMZ (based on Stupp protocol) starting 4 to 6 weeks after surgery per institution standard practice.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
147
irinotecan-ChemoSeed implementation into the resection cavity after surgical resection of GBM
Part 1 To determine the optimal Dose of Irinotecan (RP2D) to be administered for Part 2.
Time frame: 13 months
Part 2. Determination Of Progression Free Survival (PFS) to demonstrate the superiority of irinotecan-ChemoSeed compared to concurrent to SoC treatment
To demonstrate superiority of irinotecan-ChemoSeed concurrent to SoC treatment and administered into the resection margin following maximal safe surgical resection relative to SoC treatment alone, by assessment of progression-free survival (PFS).
Time frame: 39 months
Overall Response Rate (ORR)
ORR at 6 months by MRI using RANO 2.0 criteria, by independent central review and by investigator assessment.
Time frame: 6 months from recruitment
Disease Control Rate (DCR)
DCR at 12 months by MRI using RANO 2.0 by independent central review and investigator assessment.
Time frame: 12 months from recruitment
Overall Survival
Comparison of Median OS for control and treated arms
Time frame: 39 months
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