Radiodynamic Therapy (RDT) With Gliolan in Patients With First Recurrence of Brain Tumor

Inclusion Criteria:

• Written patient consent after comprehensive information

• Age >/= 18 years

• Recurrence of supratentorial glioblastoma after initial resection and adjuvanttherapy (e.g. radio-chemotherapy, targeted therapies, antiangiogenic therapies asdetermined by the tumor board) (with planned second resection cohort 0 and 1),second or third recurrences permitted

• Clinically indicated further radiotherapy as per decision of the tumor board as partof therapy for recurrence

• Histological verification of recurrent glioblastoma independent of methylated MGMTpromotor status when alkylating chemotherapy failed at this time.

• Karnofsky Performance Score ≥ 60

• For female and male patients and their female partners of childbearing/reproductivepotential(*): Willingness to apply highly effective contraception (Pearl index <1)during the entire study (and for at least 6 months after the first application of 5-ALA). Such methods include:

1. combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation: I. oral II. intravaginal III.transdermal

2. progestogen only hormonal contraception associated with inhibition ofovulation: I. oral II. injectable III. implantable

3. intrauterine device (IUD)

4. intrauterine hormone-releasing system (IUS)

5. bilateral tubal occlusion

6. vasectomised partner

7. male patients have to use a condom

8. sexual abstinence

• Pre-menopausal(*) female patients with childbearing potential: a negative pregnancytest must be obtained max. 72h prior to treatment start

• Adequate liver function: bilirubin < 1.5 times above upper limit of normal range (ULN), alanine transaminase (ALT/SGPT) and aspartate transaminase (AST/SGOT) < 3times ULN. In the case of documented or suspected Gilbert's disease bilirubin < 3times ULN.

• Adequate renal function: creatinine < 3 times above ULN; eGFR >/= 60 ml/min, Bloodclotting: INR/Quick/PT and PTT within acceptable limits according to theinvestigator.

(*) Definition: A man is considered of reproductive potential after puberty unless permanently sterile by bilateral orchidectomy. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.

Exclusion Criteria:

• Patient unable to undergo imaging by MRI, PET or contrast-enhanced CT for whateverreason (e.g. pace-maker)

• Pregnant and breastfeeding women

• Past medical history of diseases with poor prognosis, e.g., severe coronary heartdisease, heart failure (NYHA III/IV), severe and poorly controlled diabetes, immunedeficiency, residual deficits after stroke, severe mental retardation or otherserious concomitant systemic disorders incompatible with the study (at thediscretion of the investigator)

• Any active infection (at the discretion of the investigator)

• Hypersensitivity against porphyrins

• Known diagnosis of porphyria

• Participation in another clinical trial with therapeutic intervention or use of anyother therapeutic interventional agent other than the standard therapy sincediagnosis of glioblastoma

• Known intolerance to study medication

• Pre-treatment with other potentially phototoxic or photosensitizing substances (e.g.tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts, productscontaining St. John's wort ) during the 2 weeks preceding RDT