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

photonamic

Status and phase

Enrolling

Phase 2

Conditions

Glioblastoma

Treatments

Drug: 5-aminolevulinic acid

Study type

Interventional

Funder types

Industry

Identifiers

NCT03897491

GL 01

Details and patient eligibility

About

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.

Enrollment

20 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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.