Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma (NOA11)

• ClinicalTrials.gov Identifier: NCT04469699
• Recruitment Status: Recruiting
• First Posted: July 14, 2020
• Last Update Posted: December 21, 2022
• Sponsor: University Hospital Muenster
• Collaborators: Deutsche Krebshilfe e.V., Bonn (Germany); photonamic GmbH & Co. KG; medac GmbH; LifePhotonic GmbH
• Information provided by (Responsible Party): University Hospital Muenster

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme, Adult	Drug: Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid; Procedure: Stereotactic biopsy	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Controlled Clinical Trial to Evaluate the Safety and Efficacy of Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma
• Actual Study Start Date: April 12, 2021
• Estimated Primary Completion Date: April 2026
• Estimated Study Completion Date: April 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment arm; Stereotactic biopsy followed by stereotactical photodynamic therapy	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).; Other Name: Gliolan, 5-aminolevulinic acid
Control arm; Stereotactic biopsy	Procedure: Stereotactic biopsy; Stereotactic biopsy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).

Outcome Measures

Primary Outcome Measures :

1. Progression free survival (PFS) [ Time Frame: 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 :

1. 6-month PFS rate [ Time Frame: 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
2. Overall survival (OS) [ Time Frame: 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
3. Progression free time [ Time Frame: 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)
4. 12-month OS rate [ Time Frame: 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
5. 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 [ Time Frame: 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 ]
6. 48h response rate on MRI (Complete Remission, Partial Remission, Stable Disease) after treatment with iPDT (interstitial photodynamic therapy) [ Time Frame: 26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT) ]
   Response is assessed according to the RANO criteria
7. 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) [ Time Frame: 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 ]
8. Change in KPS (Karnofsky Performance Score) [ Time Frame: 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.
9. Change in NIHSS (National Institutes of Health Stroke Scale) [ Time Frame: 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.
10. Change in MMSE (Mini-Mental State Examination) [ Time Frame: 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.
11. Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery [ Time Frame: 26 to 48 hours after stereotactic intervention ]
12. Frequency of Adverse Events [ Time Frame: over the entire study period of each patient (at least 1.5 years and a maximum of 5 years) ]
13. Change in the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire) score during study participation [ Time Frame: 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 ]
14. 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 [ Time Frame: 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Juliane Schroeteler, Dr. med.; +491733802878; juliane.schroeteler@ukmuenster.de

Locations

Germany

Medizinische Fakultät Carl Gustav Carus, Klinik und Poliklinik für Neurochirurgie; Recruiting

Dresden, Germany, 01307

Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Abteilung Funktionelle NC & Stereotaxie; Recruiting

Düsseldorf, Germany, 40225

Universitätsklinikum Essen, Klinik für Neurochirurgie und Wirbelsäulenchirurgie; Recruiting

Essen, Germany, 45122

LMU München, Campus Großhadern, Neurochirurgische Klinik und Poliklinik; Not yet recruiting

München, Germany, 81377

Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie; Recruiting

Münster, Germany, 48149

Sponsors and Collaborators

University Hospital Muenster

Deutsche Krebshilfe e.V., Bonn (Germany)

photonamic GmbH & Co. KG

medac GmbH

LifePhotonic GmbH

Investigators

• Principal Investigator: Walter Stummer, Univ.-Prof. Dr. med.; University Hospital Muenster, Klinik und Poliklinik für Neurochirurgie

More Information

• Responsible Party: University Hospital Muenster
• ClinicalTrials.gov Identifier: NCT04469699
• Other Study ID Numbers: UKM12_0017; 2015-002727-25 ( EudraCT Number )
• First Posted: July 14, 2020
• Last Update Posted: December 21, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Aminolevulinic Acid; Photosensitizing Agents; Dermatologic Agents