Clinical and translational controlled study of Perampanel treatment around Surgery in patients with progressive glioblastoma (PerSurge)

INTERVENTION: Product Name: Füllstoff DAC in hard gelatine capsules is used as placebo. Füllstoff DAC consists of mannitol 99.5 % and colloidal Silicon Dioxide 0.5 %.,Product Code: N/A,Pharmaceutical Form: N/A,Other descriptive name: N/A,Strength: N/A,Pharmaceutical form of the placebo: N/A,Product Name: Fycompa 2 mg film‐coated tablets,Product Code: PRD4442834,Pharmaceutical Form: FILM‐COATED TABLET,Other descriptive name: ,Strength: Perampanel 2mg CONDITION: MedDRA version: 20.0Level: PTClassification code: 10018336Term: GlioblastomaSystem Organ Class: 100000004864 Progressive Glioblastoma ; MedDRA version: 20.0Level: PTClassification code: 10018336Term: GlioblastomaSystem Organ Class: 100000004864 Therapeutic area: Diseases [C] ‐ Neoplasms [C04] PRIMARY OUTCOME: Main Objective:The primary aim of the trial is to demonstrate the efficacy of pre‐surgical perampanel compared; to placebo treatment with respect to; A) the shift of mRNA expression patterns to a lower connectivity score in tumour tissue,; and; B) the presurgical tumour growth rate as assessed by tumour volume [cm³] per a central blinded; independent review committee (BIRC) based on AI‐quantified MRI parameters (T2/FLAIRweighted; images); in patients with recurrent/progressive glioblastoma willing to adhere to the randomised treatment; and who will undergo surgery. Primary end point(s):A) Connectivity score determined in RNA Seq from tumour tissue (tumour cryosamples),B) Kinetics in T2/FLAIR signal abnormality volume by central AI‐based MRI assessment per BIRC [from baseline to pre‐surgical resection] Secondary Objective:kinetics in contrast‐enhancing (T1CE images) tumour volume by central AI‐based MRI assessment per BIRC [pre‐surgical; postsurgical ],kinetics in tumour volume (T2/FLAIR) by central AI‐based MRI assessment per the BIRC [postsurgical],health‐related quality of life (HRQoL) and symptoms as assessed by the EORTC QLQ‐C30 and QLQ‐BN20 patient questionnaires,,severity of cognitive impairment as assessed by the mini‐mental state examination (MMSE),overall survival (OS),progression‐free survival (PFS) (from randomisation until progression according to RANO criteria),epileptic seizure activity,To check for the occurrence of the adverse effects reported in the summary of the medical product characteristics (SmPC) of the drug and to compare between both treatments. SECONDARY OUTCOME: Secondary end point(s):EORTC QLQ‐C30, QLQ‐BN20: absolute change from baseline at POD30 in the C30 summary score (according to EORTC manual; with higher scores indicating worse symptoms) Secondary end point(s):imaging‐based PFS defined as time from date of randomisation to date of first documented radiographic progression (according to the RANO criteria37,38 and Appendi XA2) which include observer‐blinded MRI‐based assessments and clinical stability) or date of death due to any cause, whichever occurs first. Secondary end point(s):MMSE: absolute change from baseline at POD30 in total MMSE score. Secondary end point(s):occurrence of side effects (AE, SAE, SUSARs) until 3 days after end of treatment (adverse events will be coded using MedDRA). Secondary end point(s):OS defined as the time from the date of randomisation to the date of death due to any cause. Secondary end point(s):post‐surgical log‐transformed tumour volume [cm³] per the BIRC based on AI‐quantified MRI parameters, incorporating the volumes from peri‐tumoral T2/FLAIR signal abnormality, excluding those areas showing ischemia (based on DWI) [on immediate postoperative MRI to day 60 post‐randomisation, i.e. POD0‐3 to POD30] Secondary end point(s):pre‐surgical and post‐surgical log‐transformed tumour volume [cm³] per the BIRC based on AIquantified MRI parameters (T1CE images) [day 0 to day 30 prior to surgery; post‐surgical: POD0 to POD30] Secondary end point(s):total number of epileptic seizures (irrespective of severity and duration) between baseline and POD30 INCLUSION CRITERIA: Histologically confirmed glioblastoma, progressive or recurrent after 1 or 2 lines of prior treatment, involving one radiotherapy and drug treatments according to institutional standards or prior trial participation, >3 months after end of radiotherapy, and therapy for relapse not yet started.,Cognitive state to understand rationale, necessity and individual consequences of study therapy and procedures.,Female patients with reproductive potentiala must use an approved contraceptive method during and for 4 weeks after the end of trial medication (Pearl Inde X<1%),Female patients with reproductive potential: a negative serum pregnancy test (beta‐ HCG) must be obtained prior to treatment start.,Indication for surgical resection of progressive or recurrent tumour tissue, with a safe waiting interval of up to 5 weeks.,A sufficient amount of resected tumour tissue (minimum 0.5 cm3) is expected to be available for the trial‐specific molecular, morphological, functional and