Glioblastoma Multiforme, Adult
Conditions
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.
Interventions
DRUGStereotactic 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).
PROCEDUREStereotactic biopsy
Stereotactic biopsy. All patients will receive further treatment of recurrent glioblastoma at the investigator´s discretion (best possible care).
Sponsors
Deutsche Krebshilfe e.V., Bonn (Germany)
photonamic GmbH & Co. KG
medac GmbH
LifePhotonic GmbH
University Hospital Muenster
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
| 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 |
| 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 |
| 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 | — |
| 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 |
| 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. |
| 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 | — |
| 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. |
Countries
Germany
Outcome results
None listed