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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma Multiforme, Adult
• Intervention / Treatment: Drug: Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid; Procedure: Stereotactic biopsy

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Juliane Schroeteler, Dr. med.; Phone Number: +491733802878; Email: juliane.schroeteler@ukmuenster.de

Study Locations

• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Medizinische Fakultät Carl Gustav Carus, Klinik und Poliklinik für Neurochirurgie
  • Düsseldorf, Germany, 40225
    • Recruiting
    • Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Abteilung Funktionelle NC & Stereotaxie
  • Essen, Germany, 45122
    • Recruiting
    • Universitätsklinikum Essen, Klinik für Neurochirurgie und Wirbelsäulenchirurgie
  • München, Germany, 81377
    • Not yet recruiting
    • LMU München, Campus Großhadern, Neurochirurgische Klinik und Poliklinik
  • Münster, Germany, 48149
    • Recruiting
    • Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Gliolan, 5-aminolevulinic acid
Other: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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)	Response is assessed according to the RANO criteria	26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT)
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)	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
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
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
Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery		26 to 48 hours after stereotactic intervention
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
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

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Collaborators: 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

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Anticipated): April 1, 2026
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: July 8, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid
• Other Study ID Numbers: UKM12_0017; 2015-002727-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No