Clinical trial NCT05736406: A Dose-escalation Clinical Study of Intraoperative Photodynamic Therapy of Glioblastoma
Official title: An Interventional, Non-randomized, 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Primary Glioblastoma
Keywords: Glioma
Glioblastoma
High Grade Glioma
Lead sponsor: Hemerion Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-02-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 model.The dose of light will be escalated in successive cohorts of patients. The starting dose is at 200 J/cm2. Enroll 3 patients at the first dose level and proceed to the next higher dose level with a cohort of 3 patients until at least 1 patient experiences a dose-limiting toxicity (DLT).
Primary purpose: TREATMENT

Brief summary: The primary objective of this clinical trial is to determine the safety and tolerability of two doses of light in intraoperative PDT added to standard of care; temozolomide-based chemotherapy in male and female patients aged 18 to 75 with newly diagnosed glioblastoma.

This treatment will be carried out in addition to the maximal surgical resection. Data collected during this trial will be used to design the upcoming pivotal study .

The study will utilize an independent Data and Safety Monitoring Board (iDSMB) that will review safety data to allow dose escalation.

Detailed description: This study is a non randomized, open label, single center , 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.

Eligibility criteria: Inclusion criteria

1. 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.
2. Signed informed consent which includes compliance with requirements and restrictions listed in the informed consent.
3. Newly diagnosed GBM (grade IV malignant high-grade glioma), presumed on the basis of clinical and MRI criteria (intra-axial brain tumor with peripheral rim contrast enhancement)
4. Karnofsky Performance Scale ≥ 70
5. Eligible for surgery
6. Amenable to maximal tumor resection based on MRI.
7. Planned to receive SOC (i.e., Stupp Protocol) treatment after surgery.
8. Ability to take oral medications.

Exclusion criteria

1. Patients with radiographic tumors of/or involving unresectable midline, basal ganglia, or brain stem as assessed by MRI
2. Patients with prior brain surgery other than stereotactic biopsy 2. Patient with Lynch syndrome 3. Patient with Li-Fraumeni syndrome 4. Debilitating cardiopulmonary disease, unstable Type 1 or Type 2 diabetes (treated or not) 5. 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 6. Clinically significant abnormal ECG results, including a corrected QT interval QTc \> 480 ms 7. Creatinine clearance \< 60 mL/min 8. Severe hepatic impairment (bilirubin \> 1.5 x the upper limit of normal \[ULN\] or alkaline phosphatase or transaminases (AST, ALT) \> 2.5 x ULN) 9. Known allergic reactions to silicone 10. Known allergic reactions or hypersensitivity to egg, soya, or peanut proteins.

   11. Febrile illness 12. 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 and tetracyclines, andtopical 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 13. Contraindication to MRI examination (e.g., MRI-incompatible pacemaker) 14. Treatment with another investigational drug or intervention within 30 days prior to or during the entire study 15. Predictable non-compliance with the rules for preventing the transient risk of skin photosensitization.

16. Clinical follow up not possible for psychological, family, social, or geographic reasons.

17. Legal incapacity 18. Pregnancy or lactation 19. Women of childbearing potential (WOCBP) and males with WOCBP partners not willing to use an effective contraceptive method from inclusion until end of study.

Primary outcomes:
measure: Maximal Tolerated Dose (MDT) of light for Photodynamic Therapy
timeFrame: 4 weeks after intervention
Secondary outcomes:
measure: Treatment response / Progression-free survival (PFS)
timeFrame: Up to 6 months after intervention
measure: Number of Adverse Events and Serious Adverse Events (Safety and Tolerability)
timeFrame: 6 months
Other outcomes:
measure: Usability of the Heliance® Solution in the operating room
timeFrame: During Procedure
Locations:
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer center
state: Pennsylvania
Study officials:
affiliation: UPMC Presbyterian Shadyside Hospital, Pittsburgh, PA
name: Jan Drappatz, MD
role: PRINCIPAL_INVESTIGATOR
References: