pd l 506 for stereotactic interstitial photodynamic therapy of newly diagnosed supratentorial idh wild-type glioblastoma

Conditions: Glioblastoma

Summary: the trial is an open, multicenter, explorative, pilot phase ii study in a small number of patients to assess safety and efficacy of stereotactic interstitial photodynamic therapy (ipdt) with pd l 506 in newly diagnosed supratentorial idh wild-type glioblastoma.


Eligibility criteria:
inclusion criteria: * biopsy proven, newly diagnosed, supratentorial, unifocal, lobar located idh wild-type glioblastoma according to the criteria of the 2016 who classification. * not safely and/or not completely resectable, lobar located, unifocal, supratentorial idh wild-type glioblastomas with a largest diameter ≤ 40 mm (largest diameter of the contrast enhanced tumor, as defined by enhanced t1 mri sequences) are eligible in case of corresponding tumor board re-estimations. * potentially completely resectable, lobar located, unifocal, supratentorial, idh wild-type glioblastoma with a largest diameter ≤ 40 mm are eligible in case of both patient's informed preference in favour of ipdt and corresponding tumor board recommendations. * age 18 - 70 years * karnofsky performance status (kps) of ≥ 70 % * minimal life expectancy of 3 months. * patients eligible for radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide: adequate haematological function (absolute neutrophil count (anc) \> 1.5 x 109/l, platelet count \> 100 x 109/l, haemoglobin \> 10 g/dl (may be transfused to maintain or exceed this level)). * international normalized ratio (inr) or pt (secs) and activated partial thromboplastin time (aptt) ≤ 1,5 times of the upper limit of normal in the laboratory where it was measured. * negative pregnancy test in fertile women * for female and male patients of reproductive potential: willingness to apply highly effective contraception (pearl index \<1) during the entire study. such methods include : * combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: * oral * intravaginal * transdermal * progestogen-only hormonal contraception associated with inhibition of ovulation : * oral * injectable * implantable * intrauterine device (iud) * intrauterine hormone-releasing system (ius) * bilateral tubal occlusion * vasectomised partner * sexual abstinence • written informed consent has been signed and dated prior to or at the beginning of visit -1 exclusion criteria: * glioblastomas involving the basal ganglia, the corpus callosum, the primary motor cortex, the ventricular system, multifocal tumors, and those involving the brain stem and/or the cerebellum. * glioblastomas exceeding the 40 mm threshold in their largest diameter * simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts) * hypersensitivity against porphyrins * known diagnosis of porphyria * acute or chronic hepatic diseases (levels of asat, alat and/or gamma-gt more than 2.5 times the upper limit of normal in the laboratory where it was measured) * manifest renal diseases with renal dysfunction (serum creatinine level \> 1.5 times of the upper limit of normal in the laboratory where it was measured) * severe, active co-morbidity: * unstable angina and/or congestive heart failure within the last 6 months * transmural myocardial infarction within the last 6 months * history of stroke, cerebral vascular accident, or transient ischemic attack within 6 months * serious and inadequately controlled cardiac arrhythmia * significant vascular disease (e.g. aortic aneurysm) * evidence of bleeding diathesis or coagulopathy * acute bacterial or fungal infections * acute exacerbation of chronic obstructive pulmonary disease * hepatic insufficiency resulting in clinical jaundice and/or coagulopathy * acquired immune deficiency syndrome; note, however, that hiv testing is not required for study entry. * inability to undergo mri (e.g., presence of a pacemaker) * known intolerance to study medication * dementia or psychic condition that might interfere with the ability to understand the study and thus give a written informed consent * simultaneous participation in another clinical study or participation in another clinical study in the 30 days directly preceding treatment or within 5 plasma half-life of the preceding study drug, whatever is longer. * pregnancy or breastfeeding * in case of both complete absence of intra-operative fluorescence between any of the inserted light diffusers and absence of significant surgery-associated bleedings (i.e. light transmission is detectable between at least two of the inserted light diffusers), the tumor will be classified as 'fluorescence-negative tumor'. ipdt will however be performed. regarding efficacy evaluation, patients with fluorescence-negative tumors will be excluded from pp-, but included in the itt-evaluation, and will be evaluated regarding safety.