Glioblastoma
Conditions
Brief summary
The trial is an open, multicenter, explorative, pilot phase II study in a small number of patients to assess safety and efficacy of stereotactic interstitial photodynamic therapy (iPDT) with PD L 506 in newly diagnosed supratentorial IDH wild-type glioblastoma.
Interventions
5-aminolevulinic acid powder for oral solution
Sponsors
photonamic GmbH & Co. KG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy proven, newly diagnosed, supratentorial, unifocal, lobar located IDH wild-type glioblastoma according to the criteria of the 2016 WHO classification. * Not safely and/or not completely resectable, lobar located, unifocal, supratentorial IDH wild-type glioblastomas with a largest diameter ≤ 40 mm (largest diameter of the contrast enhanced tumor, as defined by enhanced T1 MRI sequences) are eligible in case of corresponding tumor board re-estimations. * Potentially completely resectable, lobar located, unifocal, supratentorial, IDH wild-type glioblastoma with a largest diameter ≤ 40 mm are eligible in case of both patient's informed preference in favour of iPDT and corresponding tumor board recommendations. * Age 18 - 70 years * Karnofsky Performance status (KPS) of ≥ 70 % * Minimal life expectancy of 3 months. * Patients eligible for radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide: Adequate haematological function (Absolute neutrophil count (ANC) \> 1.5 x 109/L, Platelet count \> 100 x 109/L, Haemoglobin \> 10 g/dL (may be transfused to maintain or exceed this level)). * International normalized ratio (INR) or PT (secs) and activated partial thromboplastin time (aPTT) ≤ 1,5 times of the upper limit of normal in the laboratory where it was measured. * Negative pregnancy test in fertile women * For female and male patients of reproductive potential: Willingness to apply highly effective contraception (Pearl index \<1) during the entire study. Such methods include : * combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: * oral * intravaginal * transdermal * progestogen-only hormonal contraception associated with inhibition of ovulation : * oral * injectable * implantable * intrauterine device (IUD) * intrauterine hormone-releasing system (IUS) * bilateral tubal occlusion * vasectomised partner * sexual abstinence • Written informed consent has been signed and dated prior to or at the beginning of Visit -1
Exclusion criteria
* Glioblastomas involving the basal ganglia, the corpus callosum, the primary motor cortex, the ventricular system, multifocal tumors, and those involving the brain stem and/or the cerebellum. * Glioblastomas exceeding the 40 mm threshold in their largest diameter * Simultaneous use of other potentially phototoxic substances (e.g. tetracyclines, sulfonamides, fluoroquinolones, hypericin extracts) * Hypersensitivity against porphyrins * Known diagnosis of porphyria * Acute or chronic hepatic diseases (levels of ASAT, ALAT and/or gamma-GT more than 2.5 times the upper limit of normal in the laboratory where it was measured) * Manifest renal diseases with renal dysfunction (serum creatinine level \> 1.5 times of the upper limit of normal in the laboratory where it was measured) * Severe, active co-morbidity: * Unstable angina and/or congestive heart failure within the last 6 months * Transmural myocardial infarction within the last 6 months * History of stroke, cerebral vascular accident, or transient ischemic attack within 6 months * Serious and inadequately controlled cardiac arrhythmia * Significant vascular disease (e.g. aortic aneurysm) * Evidence of bleeding diathesis or coagulopathy * Acute bacterial or fungal infections * Acute exacerbation of chronic obstructive pulmonary disease * Hepatic insufficiency resulting in clinical jaundice and/or coagulopathy * Acquired immune deficiency syndrome; note, however, that HIV testing is not required for study entry. * Inability to undergo MRI (e.g., presence of a pacemaker) * Known intolerance to study medication * Dementia or psychic condition that might interfere with the ability to understand the study and thus give a written informed consent * Simultaneous participation in another clinical study or participation in another clinical study in the 30 days directly preceding treatment or within 5 plasma half-life of the preceding study drug, whatever is longer. * Pregnancy or breastfeeding * In case of both complete absence of intra-operative fluorescence between any of the inserted light diffusers and absence of significant surgery-associated bleedings (i.e. light transmission is detectable between at least two of the inserted light diffusers), the tumor will be classified as 'fluorescence-negative tumor'. iPDT will however be performed. Regarding efficacy evaluation, patients with fluorescence-negative tumors will be excluded from PP-, but included in the ITT-evaluation, and will be evaluated regarding safety.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the incidence of treatment-emergent Adverse Events (safety and tolerability) of iPDT with PD L 506 in adult patients with newly diagnosed supratentorial IDH wild-type glioblastoma. | 2 weeks | The incidence of treatment-emergent Adverse Events (TEAEs) of CTC grades 3, 4 and 5 within two weeks following iPDT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival rate at 12 months | 12 months | Percentage of patients without tumor progression 12 months after iPDT |
| Overall survival rate at 12 months | 12 months | Percentage of patients who are alive 12 months after iPDT |
| Progression-free survival | From date of iPDT until the date of first documented progression, up to 66 months | Time until first tumor progression |
| Overall survival | From date of iPDT until the date of death from any cause, up to 66 months | Time until death from any cause |
| MGMT promoter methylation status of the patient | Baseline | Analytical results for MGMT promoter methylation status (methylated/unmethylated) in the respective tumor samples of each patient |
| Immune status of the patient | Baseline, 2 days, 2 weeks after iPDT and then every 3 months, up to 66 months | Analytical results for immune parameters (PBMC, CD4+, CD8+) in the respective blood samples of each patient |
| Results of investigator's assessment of patient's physical condition using Karnofsky performance status scale | Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months | To determine patient's physical condition using Karnofsky performance status scale ranging from 0% (worst outcome) to 100% (best outcome) |
| Results of investigator's assessment of patient's mental condition using Mini-mental State Examination | Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months | To determine patient's mental condition using Mini-mental State Examination scale ranging from 0 (worst outcome) to 30 (best outcome) |
| Results of investigator's assessment of patient's mental condition using National Institutes of Health Stroke Scale | Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months | To determine patient's mental condition using National Institutes of Health Stroke Scale ranging from 0 (best outcome) to 34 (worst outcome) |
| Results of investigator's assessment of patient's condition using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients Questionnaire (QLQ-C30) together with the Brain module (BN20) | Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months | To determine patient's quality of life |
| Interstitial light transmittance and fluorescence data recorded | during iPDT treatment (up to 1 hour) | To determine whether correlations exist between length of OS/PFS and spectral online-monitoring measurement results (transmission and fluorescence measurements) |
| Interstitial fluorescence data recorded | during iPDT treatment (up to 1 hour) | To determine the rate of patients with fluorescence-negative tumors |
| Percentage of cylindrical diffusor laser probes without kinks, cracks etc. before and after iPDT for patients treated under protocol versions prior to V7.0 | Day 0 (Treatment day), directly before and after iPDT | Assessing the safety and performance of the insertion of Cylindrical Diffusor Laser Probes into the brain for iPDT of brain tumors for patients treated under protocol versions prior to V7.0. |
| Percentage of guiding catheters without kinks, cracks etc. before and after iPDT | Day 0 (Treatment day), directly before and after iPDT | Assessing the safety and performance of the insertion of guiding catheters into the brain for iPDT of brain tumors |
| Percentage of iPDT treatments in which the laser system works properly as planned. | Day 0 (Treatment day), directly after iPDT | Assessing safety and performance of the laser system for iPDT of brain tumors. |
| Percentage of fibers/laser ports which show a maximum deviation in the output power of less than +/-10% to the pre-defined output power of 200 mW/cm diffusor length. | Day 0 (Treatment day), directly after iPDT | Assessing safety and performance of the combination of ML7710i laser system and Cylindrical Diffusor Laser Probes for the iPDT of brain tumors. |
Countries
Germany
Contacts
PRINCIPAL_INVESTIGATORWalter Stummer, Prof. Dr.
Universitätsklinikum Münster
Outcome results
None listed