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

Prior treatment

• Concomitant intake of enzyme-inducing antiepileptic drugs (EIAEDs: carbamazepine, eslicarbazepine, oxcarbazepine, phenobarbital, phenytoin, primidon, rufinamid)
• Steroid intake of more than 4 mg dexamethasone (or equivalence dose) in the last week, or expected indication for it in the foreseeable future
• Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.
• The presence of any other concomitant severe, progressive, or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, or psychiatric disease, or signs or symptoms thereof, that may affect the subject’s participation in the study, according to investigators judgement.
• Any continued or planned standard or experimental treatment for the tumour other than resection, including antiangiogenic therapy (such as Bevacizumab), and local therapy in addition to the planned resection, including BCNU wafers, loco-regional hyperthermia, tumour bed irradiation, and photodynamic therapy.
• Any prior treatment with perampanel
• Contraindication against treatment with perampanel

Other illness

• History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 2 years unless the patient has been disease-free for 2 years.
• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
• Inability to undergo surgery (e.g. because of need for continuous anticoagulation, known bleeding disorders, thrombocytopenia <50/nl, pre-existing wound healing problems).
• Known active tuberculosis; HIV infection or active Hepatitis B (HBV) or Hepatitis C (HCV infection, or active infections requiring oral or intravenous antibiotics or that can cause a severe disease and pose a severe danger to lab personnel working on patients’ blood or tissue (e.g. rabies).

Lab values

• Severe or significant abnormal (≥ Grade 3 CTCAE v5.0) laboratory values for haematology (Hb, WBC, neutrophils, or platelets), liver (serum bilirubin, ALT, or AST) or renal function (serum creatinine).

Other

• Participation in other ongoing interventional clinical trials.
• Pregnancy or breastfeeding
• Inability to undergo contrast-enhanced MRI.
• Tumour carries a known mutation in the IDH1 or IDH2 gene

• 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 Index <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 perampanel level analysis.
• Tumour progression according to RANO criteria
• Age ≥18 years
• Karnofsky Performance status score (KPS) ≥ 60%
• Life expectancy > 3 months
• Willing and able to comply with regular neurocognitive and health-related quality of life tests/questionnaires.
• Written informed consent