Patient case: 50-year-old male with glioblastoma; genetic feature: IDH1 (R132H)

Clinical trial: PD L 506 for Stereotactic Interstitial Photodynamic Therapy of Newly Diagnosed Supratentorial IDH Wild-type Glioblastoma

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: 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 prior to or at 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
  -  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.

Relevance to patient case: possibly relevant