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

Phase 2

Recruiting

• Conditions: C71; Malignant neoplasm of brain

• Registration Number: DRKS00020543
• Lead Sponsor: photonamic GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-29
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 20

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:
o oral
o intravaginal
o transdermal
- progestogen-only hormonal contraception associated with inhibition of ovulation :
o oral
o injectable
o 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.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine safety and tolerability of iPDT with PD L 506 in adult patients with newly diagnosed supratentorial IDH wild-type glioblastoma. <br>Primary parameter: The incidence of treatment-emergent Adverse Events (TEAEs) of CTC grades 3, 4 and 5 within two weeks following iPDT.<br>[time frame: 2 weeks]