Clinical trial NCT04469699: Stereotactical Photodynamic Therapy With 5-aminolevulinic Acid (Gliolan®) in Recurrent Glioblastoma
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glioblastoma Multiforme, Adult
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Deutsche Krebshilfe e.V., Bonn (Germany)
name: photonamic GmbH & Co. KG
name: medac GmbH
name: LifePhotonic GmbH
First posted: 2020-07-14
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: through study completion (at least 1.5 years and a maximum of 5 years) or until progression or death
Secondary outcomes:
measure: 6-month PFS rate
timeFrame: for each patient up to 6 months after randomization or until progression has occurred
measure: Overall survival (OS)
timeFrame: through study completion (at least 1.5 years and a maximum of 5 years) or until death
measure: Progression free time
timeFrame: through study completion (at least 1.5 years and a maximum of 5 years) or until progression
measure: 12-month OS rate
timeFrame: for each patient up to 12 months after randomization or until death
measure: 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
timeFrame: 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
measure: 48h response rate on MRI (Complete Remission, Partial Remission, Stable Disease) after treatment with iPDT (interstitial photodynamic therapy)
timeFrame: 26 - 48 hours after stereotactic procedure in patients treated with interstitial photodynamic therapy (iPDT)
measure: 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)
timeFrame: 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
measure: Change in KPS (Karnofsky Performance Score)
timeFrame: 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
measure: Change in NIHSS (National Institutes of Health Stroke Scale)
timeFrame: 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
measure: Change in MMSE (Mini-Mental State Examination)
timeFrame: 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
measure: Brain edema as assessed by MRI within 26 to 48 h after stereotactic surgery
timeFrame: 26 to 48 hours after stereotactic intervention
measure: Frequency of Adverse Events
timeFrame: over the entire study period of each patient (at least 1.5 years and a maximum of 5 years)
measure: Change in the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire) score during study participation
timeFrame: 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
measure: 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
timeFrame: 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
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Medizinische Fakultät Carl Gustav Carus, Klinik und Poliklinik für Neurochirurgie
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Abteilung Funktionelle NC & Stereotaxie
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Klinik für Neurochirurgie und Wirbelsäulenchirurgie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Klinik und Poliklinik für Neurochirurgie
Study officials:
affiliation: University Hospital Muenster, Klinik und Poliklinik für Neurochirurgie
name: Walter Stummer, Univ.-Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: