Clinical Trial Finder

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.

Arms

Experimental: Interstitial photodynamic therapy

20 mg 5-aminolevulinic acid per kg body weight orally four hours (range 3,5-4,5 hours) before the induction of general anaesthesia.

Interventions

Drug: - 5-aminolevulinic acid

5-aminolevulinic acid powder for oral solution