Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma

Glioblastoma Multiforme, Adult Clinical Trial

— NOA11  

Official title:

Controlled Clinical Trial to Evaluate the Safety and Efficacy of Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04469699
• Other study ID #: UKM12_0017
• Secondary ID: 2015-002727-25
• Status: Recruiting
• Phase: Phase 2
• Start date: April 12, 2021
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: University Hospital Muenster
• Contact: Juliane Schroeteler, Dr. med.
• Phone: +491733802878
• Email: juliane.schroeteler[@]ukmuenster.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this multicenter, randomized, non-blinded trial the efficacy and safety of stereotactical photodynamic therapy with 5-aminolevulinic acid will be investigated in 106 patients with recurrent glioblastoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: April 2026
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Written informed consent

2. Age 18 - 75 years

3. Karnofsky Performance Score (KPS) of =60 %

4. Radiologically suspected diagnosis (according to RANO criteria) of the first recurrence of a glioblastoma located in the cerebral hemisphere including insular and diencephalon. Tumors in the brain stem are excluded. First MRI with signs of first recurrence (radiologic RANO criteria for disease progression) within 8 weeks prior to Informed Consent. Not necessarily identical to primary tumor location

5. Single or single progressive contrast-enhancing lesion on MRI, largest diameter not more than 2.5 cm

6. For female and male patients of reproductive potential: Willingness to apply highly effective contraception (Pearl index <1) during the entire study

Exclusion Criteria:

1. Multifocal disease > 2 locations

2. Patients with significant non-enhancing tumor portions

3. Previous treatment of recurrence

4. Other malignant disease except basalioma

5. Hypersensitivity against porphyrins or Gliolan® or Fluorethylenpropylen (FEP )

6. Porphyria

7. HIV infection, active Hepatitis B or C infection

8. Bone marrow reserve:

• white blood cell (WBC) count <2000/µl,
• platelets <100000/µl,

9. Liver function:

• total bilirubin > 1.5 times above upper limit of normal range (ULN)
• alanine transaminase (ALT) and aspartate transaminase (AST) > 3 times ULN

10. Renal function:

• creatinine > 1.5 times ULN

11. Blood clotting:

• Quick/INR or PTT out of acceptable limits

12. Conditions precluding MRI (e.g. pacemaker)

13. Past medical history of diseases with poor prognosis, e.g. severe coronary heart disease, heart failure (NYHA III/IV), severe 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)

14. Any active infection (at the discretion of the investigator)

15. Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, to give informed consent or to comply with the trial protocol

16. Previous antiangiogenic treatment

17. Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial.

18. Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme, Adult

Intervention

Drug:
• Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid
5-ALA HCl orally (20 mg/kg bw) 3,5-4,5 hours prior to induction of anaesthesia for stereotactic biopsy followed by stereotactical photodynamic therapy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).

Procedure:
• Stereotactic biopsy
Stereotactic biopsy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).

Locations

Country	Name	City	State
Germany	Medizinische Fakultät Carl Gustav Carus, Klinik und Poliklinik für Neurochirurgie	Dresden
Germany	Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Abteilung Funktionelle NC & Stereotaxie	Düsseldorf
Germany	Universitätsklinikum Essen, Klinik für Neurochirurgie und Wirbelsäulenchirurgie	Essen
Germany	LMU München, Campus Großhadern, Neurochirurgische Klinik und Poliklinik	München
Germany	Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie	Münster

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital Muenster	Deutsche Krebshilfe e.V., Bonn (Germany), LifePhotonic GmbH, medac GmbH, photonamic GmbH & Co. KG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS)	Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria (Response Assessment in Neuro-Oncology Criteria) or death from any cause	through study completion (at least 1.5 years and a maximum of 5 years) or until progression or death
Secondary	6-month PFS rate	Progression free survival (PFS) measured as time from the day of randomization until diagnosis of progressive disease as determined by MRI according to RANO criteria or death from any cause	for each patient up to 6 months after randomization or until progression has occurred
Secondary	Overall survival (OS)	Overall survival (OS) measured as time from the day of randomization until death	through study completion (at least 1.5 years and a maximum of 5 years) or until death
Secondary	Progression free time	Progression free time as time from the day of randomization until progressive disease (death is regarded as censored)	through study completion (at least 1.5 years and a maximum of 5 years) or until progression
Secondary	12-month OS rate	Overall survival (OS) measured as time from the day of randomization until death	for each patient up to 12 months after randomization or until death
Secondary	Absolute changes from baseline in contrast medium volume uptake from the MRI performed 48 hours after randomization on, and during any MRI performed thereafter to monitor for disease progression		Baseline, 26 - 48 hours after stereotactic procedure, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression, and then every 3 months until end of entire study (up to 5 years) or progression
Secondary	48h response rate on MRI (Complete Remission, Partial Remission, Stable Disease) after treatment with iPDT (interstitial photodynamic therapy)	Response is assessed according to the RANO criteria	26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT)
Secondary	If a PET (positron emission tomography) was performed less than 2 weeks apart from an MRI: Consistency of both procedures with regard to the region of interest (ROI)		Baseline, 26 - 48 hours after stereotactic procedure, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression
Secondary	Change in KPS (Karnofsky Performance Score)	Minimum value: 0, maximum value: 100. A higher value means a better outcome.	Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression
Secondary	Change in NIHSS (National Institutes of Health Stroke Scale)	Minimum value: 0, maximum value: 42. A higher value means a worse outcome.	Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression
Secondary	Change in MMSE (Mini-Mental State Examination)	Minimum value: 0, maximum value: 30. A higher value means a better outcome.	Baseline, 26 -48 hours after stereotactic procedure, upon discharge or 7 days after stereotactic procedure, 1 month after randomization and then every 2 months until 1.5 years after randomization or disease progression
Secondary	Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery		26 to 48 hours after stereotactic intervention
Secondary	Frequency of Adverse Events		over the entire study period of each patient (at least 1.5 years and a maximum of 5 years)
Secondary	Change in the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire) score during study participation		Baseline, at discharge or 7 days after intervention, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression
Secondary	Change in the EORTC QLQ-BN20 module (European Organisation for Research and Treatment of Cancer Quality of Life Brain Cancer Module) score during study participation		Baseline, at discharge or 7 days after intervention, 1 month after randomization and then every 2 months, 1.5 years after randomization or at disease progression and then every 3 months until end of entire study (up to 5 years) or progression