An interventional, multicenter, and international phase 1/2, light-dose-escalation study to investigate the safety and feasibility of intraoperative photodynamic therapy (PDT) with Pentalafen® drug and Heliance® Solution device in male and female patients 18 to 75 years of age with grade IV glioblastoma.
- Conditions
- High-grade glioma Glioblastoma
- Interventions
- Combination Product: 5-ALA HCl intraoperative Photodynamic Therapy (PDT) at 200 J/cm^2Combination Product: 5-ALA HCl intraoperative Photodynamic Therapy (PDT) at 400 J/cm^2
- Registration Number
- 2025-520563-41-00
- Lead Sponsor
- Hemerion Therapeutics
- Brief Summary
Safety and tolerability of intraoperative PDT regimen in patients with GBM by determining the MTD and the recommended dose light for the pivotal trial.
- Detailed Description
This study is a non randomized, open label, multicentercenter , phase 1/2 trial with a sequential enrollment in a 3+3 dose escalation design to establish the maximal tolerated dose of light (MTD).
The dose of light will be escalated in successive cohorts of patients until at least 1 patient experiences a dose-limiting toxicity (DLT).
A DLT is defined as any grade ≥ 3 Adverse Event (AE), or any relevant grade 2 AE of Central Nervous System or any Serious Adverse Events (SAEs) possibly, probably or definitively related to the intraoperative PDT (i.e., 5-aminolevulinic acid hydrochloride (5-ALA HCl) administration + brain cavity illumination), for which the onset date is within 28 days after the procedure, and where conservative therapy fails and surgical is required, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
After dose escalation patient will be followed in the standard of care until visit at 6 months to evaluate the progression free survival.
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 6
Males or females must be between 18, or legal age of consent, and 75 years of age (both included) at the time of signing informed consent.
Signed informed consent which includes compliance with requirements and restrictions listed in the informed consent.
Newly diagnosed GBM, presumed on the basis of clinical and MRI criteria (intra-axial brain tumor with peripheral rim contrast enhancement).
Karnofsky Performance Score ≥70
Eligible for surgery
Amenable to maximal tumor resection based on MRI
Planned to receive SOC (i.e., Stupp Protocol) treatment after surgery
Ability to take oral medications
Tumor eligible to PDT procedure as validated by both investigator and sponsor based on pre-operative MRI data
a. Patient with bifocal or multifocal disease, assessed on MR1I T1Gd enhanced. b. Patient with tumor of deep location such as tumor involving the corpus callosum, the basal ganglia, the brain stem, or tumor involving the midline as assessed on MRI. c. Patient with prior brain surgery other than stereotactic biopsy
Known allergic reactions or hypersensitivity to egg, soya, or peanut proteins.
Febrile illness
Contraindication to 5-ALA HCl administration, including: a) Porphyria b) Taking photosensitizing drugs 24 hours before and 14 days after the administration of Pentalafen® including but not limited to: St. John’s wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones, tetracyclines, and topical preparations containing ALA c) Inability to suspend a long-term hepatotoxic treatment (such as, but not limited to diclofenac, fenofibrate, carbamazepine for 24 hours after 5-ALA HCl intake.
Contraindication to MRI examination (e.g., MRI-incompatible pacemaker)
Treatment with another investigational drug or intervention within 30 days prior to or during the entire study
Predictable non-compliance with the rules for preventing the transient risk of skin photosensitization.
Clinical follow up not possible for psychological, family, social, or geographic reasons.
Legal incapacity
Pregnancy or lactation
Women of childbearing potential (WOCBP) and males with WOCBP partners not willing to use an effective contraceptive method from inclusion until end of study
Patient with Lynch syndrome
Patient with Li-Fraumeni syndrome
Debilitating cardiopulmonary disease, unstable Type 1 or Type 2 diabetes (treated or not)
History or current condition of another malignancy (excluding basal cell carcinoma, or carcinoma in-situ) unless treated and off all active therapy for more than 5 years.
Clinically significant abnormal ECG results, including a corrected QT interval QTc > 480 ms.
Creatinine clearance < 60 mL/min
Severe hepatic impairment (bilirubin > 1.5 x the upper limit of normal [ULN] or alkaline phosphatase or transaminases (AST, ALT) > 2.5 x ULN)
Known allergic reactions to silicone.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 200 J/cm^2 5-ALA HCl intraoperative Photodynamic Therapy (PDT) at 200 J/cm^2 Patient will undergo intraoperative Photodynamic therapy at 200 J/cm\^2 400 J/cm^2 5-ALA HCl intraoperative Photodynamic Therapy (PDT) at 400 J/cm^2 Patient will undergo intraoperative Photodynamic therapy at 400 J/cm\^2
- Primary Outcome Measures
Name Time Method MTD, which will be assessed on the basis of number of patients with DLT. MTD, which will be assessed on the basis of number of patients with DLT.
- Secondary Outcome Measures
Name Time Method Score of device usability calculated from usefulness, ease of use, ease of learning and satisfaction/intention of use measures. Score of device usability calculated from usefulness, ease of use, ease of learning and satisfaction/intention of use measures.
PFS6, defined as the interval (in days or months) from intraoperative PDT to the date of first detection of progressive disease. PFS6, defined as the interval (in days or months) from intraoperative PDT to the date of first detection of progressive disease.
Number of AEs and SAEs Number of AEs and SAEs
Trial Locations
- Locations (1)
Centre Hospitalier Universitaire De Lille
🇫🇷Lille Cedex, France
Centre Hospitalier Universitaire De Lille🇫🇷Lille Cedex, FranceNicolas ReynsSite contact0320444145drs.promotion@chru-lille.fr