Table 1.

Overview of visits and interventions

Study period	Enrolment	Treatment period (60 ± 3 days)					Post-treatment follow-up
	Screening/Baseline						Safety follow up	OS & PFS follow-up
Visit no.	1	2	3	4	5	6	7	FU
Timeline/Timepoint	D0	D16 (± 2)	0–3 days prior resection	D30 (± 3) tumour resection	0–3 days after resection	POD30 (± 3) EOT visit	4 weeks after last dose (EOT visit)	Every 3 months
Mode of scheduled visit	Outpatient/inpatient	Outpatient/inpatient	Outpatient/inpatient	Inpatient	Outpatient/inpatient	Outpatient/inpatient	Outpatient/inpatient	Outpatient/ tel. visit
Written Informed Consenta	X
In-/Exclusion Criteria	X
Demographics, medical and surgical history/ preexisting conditions (evaluated in analogy to CTCAE)	X
Randomisation*	X
Vital signsb	X		X			X	X
Physical and neurological examination	X	X	X		X	X	X
Concomitant medications/procedures	X	X	X	X	X	X	X	X c
Karnofsky Performance Status Scale	X	X	X		X	X	X
Mini Mental State Examination	X					X
HRQoL: Patient questionnaires EORTC QLQ-C30, QLQ-BN20	X					X
Adverse Events		X	X	X	X	X	X
Documentation of epileptic seizures	X d	X	X		X	X	X
Intervention
Dispensing of trial druge	X	X	X		X
Return of trial drug		X	X		X	X
Study drug compliance checkf		X	X	X	X	X
Tumour (MRI) and response assessment
Gd-MRI (volumetric assessment of tumour sample)g	X	X	X		X	X
Progression (RANO criteria, imaging-based)		X	X		X	X	X (if MRI performed, according to local standards)	X h
Survival status		X	X	X	X	X	X	X h
Laboratory evaluations
Haematology	X i		X		X		X
Clinical chemistry	X i		X		X		X
Pregnancy test	X		X			X
Asservation of tumour materialj, assessment of connectivity score				X
Serum perampanel concentrationk,+				X
Serum for exploratory biomarkers for network connectivity +	X			X		X
Cerebrospinal fluid (CSF)l,+	X			X
Plasma (Determination of extracellular vesicles)+				X

Bold font means assessment for derivation of one of the two primary efficacy outcomes. Tumour resection is no trial-specific procedure and no component of the intervention

*All baseline characteristics (including vital signs, laboratory data, medical history, prior medication,…) must be assessed before randomisation

⁺Exploratory/Translational research (not part of the main trial)

^aWritten informed consent can be obtained up to 7 days prior to randomisation, but before any study-specific intervention/assessment

^bVital signs: blood pressure, pulse rate, temperature

^cIn long-term FU only subsequent anticancer therapies will be documented

^dBased on the last 4 weeks

^eExperimental/ control intervention: capsules once daily before going to bed (weekly increases up to 1 × 5 capsules / day)

^fTreatment adherence (check of patient’s dosing diary and the counting of the number of returned capsules) at every study visit

^gGadolinium Magnetic Resonance Imaging; Day 0 (-4 days): reference MRI; Day 16 (± 2 days): “safety MRI” to detect patients who need earlier resection (before day 30 post-randomisation) according to the assessment of the local investigator

^hProgression determined by the investigator according to RANO without central review [AI-based]) by the BIRC, and survival status during long-term follow-up will be determined for every patient by phone interviews or by e-mail or regular patient follow-up documentations at the respective site every 3 months until last patient out

ⁱUp to 7 days prior to randomisation as part of routine laboratory analyses

^jRelapse tumour resection 30 [28–34] days after Day 0. Tissue asservation should take place 10–18 h after last study drug intake: [1] fresh frozen, [2] FFPE, [3] 4% PFA; for measurement of perampanel tissue levels and study drug-dependent tumour tissue effects. On the day prior to surgical tumour removal, the exact time of intake of trial medication has to be documented

^kSerum sample (Perampanel) is taken 10–14 h after last study drug intake

^lAt baseline, CSF is collected by lumbar puncture in a suitable plastic tube. On the day of surgery, CSF can be collected intraoperatively or by lumbar puncture