Clinical Trial Finder

Inclusion Criteria:

• - Written patient consent after comprehensive information.

• - Age >/= 18 years.

• - Recurrence of supratentorial glioblastoma after initial resection and adjuvant therapy (e.g. radio-chemotherapy, targeted therapies, antiangiogenic therapies as determined 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 part of therapy for recurrence.

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

• - Karnofsky Performance Score ≥ 60.

• - For female and male patients and their female partners of childbearing/reproductive potential(*): 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 contraception associated with inhibition of ovulation:

• I. oral II.

intravaginal

• III. transdermal.

2. progestogen only hormonal contraception associated with inhibition of ovulation:

• 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 pregnancy test 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) < 3 times ULN.

In the case of documented or suspected Gilbert's disease bilirubin < 3 times ULN.

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

(*) 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 whatever reason (e.g. pace-maker) - Pregnant and breastfeeding women.

• - Past medical history of diseases with poor prognosis, e.g., severe coronary heart disease, heart failure (NYHA III/IV), severe and poorly controlled diabetes, immune deficiency, residual deficits after stroke, severe mental retardation or other serious concomitant systemic disorders incompatible with the study (at the discretion 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 any other therapeutic interventional agent other than the standard therapy since diagnosis of glioblastoma.

• - Known intolerance to study medication.

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

Arms

Experimental: Radiodynamic therapy (RDT)

All patients will be treated with RDT. Patients are devided into cohorts which differs in the total amount and frequence of RDT.

Interventions

Drug: - Gliolan

A repetitive dose of Gliolan will be administrated in combination with radiotherapy (radiodynamic therapy)

Radiation: - Radiodynamic therapy

Radiotherapy will be performed in combination with Gliolan administration