Back to resultsStereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma (NOA11)
Primary Purpose
Glioblastoma Multiforme, Adult
Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid
Stereotactic biopsy
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma Multiforme, Adult
Eligibility Criteria
Inclusion Criteria:
- Written informed consent
- Age 18 - 75 years
- Karnofsky Performance Score (KPS) of ≥60 %
- 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
- Single or single progressive contrast-enhancing lesion on MRI, largest diameter not more than 2.5 cm
- For female and male patients of reproductive potential: Willingness to apply highly effective contraception (Pearl index <1) during the entire study
Exclusion Criteria:
- Multifocal disease > 2 locations
- Patients with significant non-enhancing tumor portions
- Previous treatment of recurrence
- Other malignant disease except basalioma
- Hypersensitivity against porphyrins or Gliolan® or Fluorethylenpropylen (FEP )
- Porphyria
- HIV infection, active Hepatitis B or C infection
Bone marrow reserve:
- white blood cell (WBC) count <2000/μl,
- platelets <100000/μl,
Liver function:
- total bilirubin > 1.5 times above upper limit of normal range (ULN)
- alanine transaminase (ALT) and aspartate transaminase (AST) > 3 times ULN
Renal function:
- creatinine > 1.5 times ULN
Blood clotting:
- Quick/INR or PTT out of acceptable limits
- Conditions precluding MRI (e.g. pacemaker)
- 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)
- Any active infection (at the discretion of the investigator)
- 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
- Previous antiangiogenic treatment
- Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial.
- Pregnancy or breastfeeding
Sites / Locations
- Medizinische Fakultät Carl Gustav Carus, Klinik und Poliklinik für NeurochirurgieRecruiting
- Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Abteilung Funktionelle NC & StereotaxieRecruiting
- Universitätsklinikum Essen, Klinik für Neurochirurgie und WirbelsäulenchirurgieRecruiting
- LMU München, Campus Großhadern, Neurochirurgische Klinik und Poliklinik
- Universitätsklinikum Münster, Klinik und Poliklinik für NeurochirurgieRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Treatment arm
Control arm
Arm Description
Stereotactic biopsy followed by stereotactical photodynamic therapy
Stereotactic biopsy
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
Overall survival (OS)
Overall survival (OS) measured as time from the day of randomization until death
Progression free time
Progression free time as time from the day of randomization until progressive disease (death is regarded as censored)
12-month OS rate
Overall survival (OS) measured as time from the day of randomization 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
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
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)
Change in KPS (Karnofsky Performance Score)
Minimum value: 0, maximum value: 100. A higher value means a better outcome.
Change in NIHSS (National Institutes of Health Stroke Scale)
Minimum value: 0, maximum value: 42. A higher value means a worse outcome.
Change in MMSE (Mini-Mental State Examination)
Minimum value: 0, maximum value: 30. A higher value means a better outcome.
Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery
Frequency of Adverse Events
Change in the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire) score during study participation
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
Full Information
NCT ID
NCT04469699
First Posted
May 12, 2020
Last Updated
December 20, 2022
Sponsor
University Hospital Muenster
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany), photonamic GmbH & Co. KG, medac GmbH, LifePhotonic GmbH
1. Study Identification
Unique Protocol Identification Number
NCT04469699
Brief Title
Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma
Acronym
NOA11
Official Title
Controlled Clinical Trial to Evaluate the Safety and Efficacy of Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 12, 2021 (Actual)
Primary Completion Date
April 2026 (Anticipated)
Study Completion Date
April 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Muenster
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany), photonamic GmbH & Co. KG, medac GmbH, LifePhotonic GmbH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme, Adult
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
106 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
Stereotactic biopsy followed by stereotactical photodynamic therapy
Arm Title
Control arm
Arm Type
Other
Arm Description
Stereotactic biopsy
Intervention Type
Drug
Intervention Name(s)
Stereotactic biopsy followed by stereotactical photodynamic therapy with 5-aminolevulinic acid
Other Intervention Name(s)
Gliolan, 5-aminolevulinic acid
Intervention Description
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).
Intervention Type
Procedure
Intervention Name(s)
Stereotactic biopsy
Intervention Description
Stereotactic biopsy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).
Primary Outcome Measure Information:
Title
Progression free survival (PFS)
Description
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
Time Frame
through study completion (at least 1.5 years and a maximum of 5 years) or until progression or death
Secondary Outcome Measure Information:
Title
6-month PFS rate
Description
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
Time Frame
for each patient up to 6 months after randomization or until progression has occurred
Title
Overall survival (OS)
Description
Overall survival (OS) measured as time from the day of randomization until death
Time Frame
through study completion (at least 1.5 years and a maximum of 5 years) or until death
Title
Progression free time
Description
Progression free time as time from the day of randomization until progressive disease (death is regarded as censored)
Time Frame
through study completion (at least 1.5 years and a maximum of 5 years) or until progression
Title
12-month OS rate
Description
Overall survival (OS) measured as time from the day of randomization until death
Time Frame
for each patient up to 12 months after randomization or until death
Title
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
Title
48h response rate on MRI (Complete Remission, Partial Remission, Stable Disease) after treatment with iPDT (interstitial photodynamic therapy)
Description
Response is assessed according to the RANO criteria
Time Frame
26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT)
Title
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
Title
Change in KPS (Karnofsky Performance Score)
Description
Minimum value: 0, maximum value: 100. A higher value means a better outcome.
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
Title
Change in NIHSS (National Institutes of Health Stroke Scale)
Description
Minimum value: 0, maximum value: 42. A higher value means a worse outcome.
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
Title
Change in MMSE (Mini-Mental State Examination)
Description
Minimum value: 0, maximum value: 30. A higher value means a better outcome.
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
Title
Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery
Time Frame
26 to 48 hours after stereotactic intervention
Title
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)
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent
Age 18 - 75 years
Karnofsky Performance Score (KPS) of ≥60 %
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
Single or single progressive contrast-enhancing lesion on MRI, largest diameter not more than 2.5 cm
For female and male patients of reproductive potential: Willingness to apply highly effective contraception (Pearl index <1) during the entire study
Exclusion Criteria:
Multifocal disease > 2 locations
Patients with significant non-enhancing tumor portions
Previous treatment of recurrence
Other malignant disease except basalioma
Hypersensitivity against porphyrins or Gliolan® or Fluorethylenpropylen (FEP )
Porphyria
HIV infection, active Hepatitis B or C infection
Bone marrow reserve:
white blood cell (WBC) count <2000/μl,
platelets <100000/μl,
Liver function:
total bilirubin > 1.5 times above upper limit of normal range (ULN)
alanine transaminase (ALT) and aspartate transaminase (AST) > 3 times ULN
Renal function:
- creatinine > 1.5 times ULN
Blood clotting:
- Quick/INR or PTT out of acceptable limits
Conditions precluding MRI (e.g. pacemaker)
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)
Any active infection (at the discretion of the investigator)
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
Previous antiangiogenic treatment
Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial.
Pregnancy or breastfeeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Juliane Schroeteler, Dr. med.
Phone
+491733802878
Email
juliane.schroeteler@ukmuenster.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter Stummer, Univ.-Prof. Dr. med.
Organizational Affiliation
University Hospital Muenster, Klinik und Poliklinik für Neurochirurgie
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medizinische Fakultät Carl Gustav Carus, Klinik und Poliklinik für Neurochirurgie
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Abteilung Funktionelle NC & Stereotaxie
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Essen, Klinik für Neurochirurgie und Wirbelsäulenchirurgie
City
Essen
ZIP/Postal Code
45122
Country
Germany
Individual Site Status
Recruiting
Facility Name
LMU München, Campus Großhadern, Neurochirurgische Klinik und Poliklinik
City
München
ZIP/Postal Code
81377
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie
City
Münster
ZIP/Postal Code
48149
Country
Germany
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma
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