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

Phase 2

Terminated

• Conditions: Glioblastoma Multiforme, Adult
• Interventions: Drug: Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid; Procedure: Stereotactic biopsy

• Registration Number: NCT04469699
• Lead Sponsor: University Hospital Muenster

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-12
• Study First Submitted QC: 2020-07-08
• Study First Posted: 2020-07-14
• Study Start: 2021-04-12
• Primary Completion: 2025-01-30
• Study Completion: 2025-01-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-06
• Last Update Posted: 2025-03-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment arm	Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid	Stereotactic biopsy followed by stereotactical photodynamic therapy
Control arm	Stereotactic biopsy	Stereotactic biopsy

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	through study completion (at least 1.5 years and a maximum of 5 years) or until progression or death	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

Secondary Outcome Measures

Name	Time	Method
6-month PFS rate	for each patient up to 6 months after randomization or until progression has occurred	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
Overall survival (OS)	through study completion (at least 1.5 years and a maximum of 5 years) or until death	Overall survival (OS) measured as time from the day of randomization until death
12-month OS rate	for each patient up to 12 months after randomization or until death	Overall survival (OS) measured as time from the day of randomization until death
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
Change in KPS (Karnofsky Performance Score)	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	Minimum value: 0, maximum value: 100. A higher value means a better outcome.
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
Progression free time	through study completion (at least 1.5 years and a maximum of 5 years) or until progression	Progression free time as time from the day of randomization until progressive disease (death is regarded as censored)
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
48h response rate on MRI (Complete Remission, Partial Remission, Stable Disease) after treatment with iPDT (interstitial photodynamic therapy)	26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT)	Response is assessed according to the RANO criteria
Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery	26 to 48 hours after stereotactic intervention
Change in NIHSS (National Institutes of Health Stroke Scale)	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	Minimum value: 0, maximum value: 42. A higher value means a worse outcome.
Change in MMSE (Mini-Mental State Examination)	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	Minimum value: 0, maximum value: 30. A higher value means a better outcome.
Frequency of Adverse Events	over the entire study period of each patient (at least 1.5 years and a maximum of 5 years)
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

Trial Locations

Locations (4)

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

Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie; 🇩🇪 Münster, Germany