Clinical trial NCT03897491: PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma
Official title: Evaluation of the Feasibility of PD L 506 for Stereotactic Interstitial Photodynamic Therapy (iPDT) in Adult Patients With Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Glioblastoma
Lead sponsor: photonamic GmbH & Co. KG
Sponsor class: INDUSTRY
First posted: 2019-04-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 2 weeks
Secondary outcomes:
measure: Progression-free survival rate at 12 months
timeFrame: 12 months
measure: Overall survival rate at 12 months
timeFrame: 12 months
measure: Progression-free survival
timeFrame: From date of iPDT until the date of first documented progression, up to 66 months
measure: Overall survival
timeFrame: From date of iPDT until the date of death from any cause, up to 66 months
measure: MGMT promoter methylation status of the patient
timeFrame: Baseline
measure: Immune status of the patient
timeFrame: Baseline, 2 days, 2 weeks after iPDT and then every 3 months, up to 66 months
measure: Results of investigator's assessment of patient's physical condition using Karnofsky performance status scale
timeFrame: Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
measure: Results of investigator's assessment of patient's mental condition using Mini-mental State Examination
timeFrame: Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
measure: Results of investigator's assessment of patient's mental condition using National Institutes of Health Stroke Scale
timeFrame: Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
measure: 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)
timeFrame: Baseline, 2 weeks after iPDT and then every 3 months, up to 66 months
measure: Interstitial light transmittance and fluorescence data recorded
timeFrame: during iPDT treatment (up to 1 hour)
measure: Interstitial fluorescence data recorded
timeFrame: during iPDT treatment (up to 1 hour)
measure: Percentage of cylindrical diffusor laser probes without kinks, cracks etc. before and after iPDT for patients treated under protocol versions prior to V7.0
timeFrame: Day 0 (Treatment day), directly before and after iPDT
measure: Percentage of guiding catheters without kinks, cracks etc. before and after iPDT
timeFrame: Day 0 (Treatment day), directly before and after iPDT
measure: Percentage of iPDT treatments in which the laser system works properly as planned.
timeFrame: Day 0 (Treatment day), directly after iPDT
measure: 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.
timeFrame: Day 0 (Treatment day), directly after iPDT
Other outcomes:
Locations:
city: Köln
country: Germany
facility: Uniklinik Köln
city: München
country: Germany
facility: Klinikum der Universität München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
Study officials:
affiliation: Universitätsklinikum Münster
name: Walter Stummer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: