Clinical Trial Evaluating Safety of 5-Aminolevulinic Acid (5-ALA) Combined With CV01 Delivery of Ultrasound for Sonodynamic Therapy (SDT) in Patients With Newly Diagnosed High-Grade Glioma (HGG) Prior to Resection and Standard Adjuvant Therapy (ALA SDT GLIOMA 401)

NCT06665724 | Completed Phase 1 DMC

• 3 other identifiers: WWU22_00322023-509238-20-00UTN: U1111-1296-1261
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is designed to evaluate safety and explore possible efficacy of 5-aminolevulinic acid hydrochloride (5-ALA HCl, Gliolan®) with CV01 delivery of ultrasound for sonodynamic therapy in patients with newly diagnosed high-grade glioma prior to resection and standard adjuvant therapy. The study will accrue 10 evaluable high-grade glioma patients. Patients who qualify will receive sonodynamic therapy (5 ALA combined with CV01-delivered sonication) 2 to 5 days prior to standard resection, with one study magnetic resonance imaging being performed between sonodynamic therapy and resection. Resection will be followed by standard radio-/chemotherapy. All patients will be followed up in-study for toxicities and adverse events for 28 days.

Conditions

Anaplastic Oligodendroglioma (AO); Glioblastoma (GBM); Anaplastic Astrocytoma (AA)

Keywords

newly diagnosed high-grade glioma; sonodynamic therapy

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability

  Clinical safety and tolerability will be assessed based on the observation of adverse events (AEs). Adverse events will be graded as per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.

  From the time the informed consent is signed until 28 days following administration of sonodynamic therapy (end of trial participation)

Secondary Outcomes (2)

• Radiological changes

  Changes from visit 1 (< 8 days before sonodynamic therapy) to visit 3 (2 to 5 days after sonodynamic therapy)

• Histopathological efficacy

  Biopsies will be collected during standard surgery.

Study Arms (1)

Sonodynamic Therapy (SDT)

EXPERIMENTAL

Patients will receive sonodynamic therapy (5 ALA combined with CV01-delivered sonication) 2 to 5 days prior to standard resection.

Drug: 5-Aminolevulinic acid Hydrochloride (Gliolan®); Device: CV01

Interventions

5-Aminolevulinic acid Hydrochloride (Gliolan®) DRUG

Patients will receive 5-Aminolevulinic acid hydrochloride via oral administration (20 mg/kg) 6-8 hours before CV01 treatment.

Sonodynamic Therapy (SDT)

CV01 DEVICE

Ultrasound will be delivered 6-8 hours after administration of 5-aminolevulinic acid hydrochloride. A total of 12 fields will be treated (10 treatment sites across the hemisphere with 2 additional treatments over areas of increased enhancement).

Sonodynamic Therapy (SDT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• WHO Performance Status of 0-2
• Patients with cranial MRI displaying typical features of high-grade glioma on imaging or histologically proven high-grade glioma including GBM, anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO). No previous tumor specific treatment such as surgery (apart from biopsy), radio- or chemotherapy, antiangiogenic or immunotherapy.
• Planned debulking or cytoreductive surgery
• The following laboratory values at study entry
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin (Hgb) \> 10g/dL
• AST and ALT ≤ 2.5 x Upper Limit of Normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Creatine clearance (CrCL) as estimated by Cockcroft-Gault equation of
• ≥ 40 mL/min
• Blood clotting within acceptable limits according to investigator
• For female and male patients and their female partners of childbearing/reproductive potential: Willingness to apply highly effective contraception (Pearl index \<1) during the entire study and in female patients for 6 months after the last application of Gliolan® and in male patients and their female partners for 3 months after the last application of Gliolan®.
• Ability to understand and provide informed consent

You may not qualify if:

• Infra-tentorial tumors
• Patients who have clinically significant edema or tumor mass effect requiring urgent intervention (e.g., surgery, initiation of steroids, escalating doses of steroids)
• Women who are pregnant or breastfeeding
• Inability to undergo MRI or receive gadolinium (Gd)
• Hypersensitivity to 5-ALA or porphyrins
• Average skull thickness at the treatment field \> 10 mm from standard navigation CTs. The treatment field is defined as the various locations on the head where the transducer will be coupled to the patient. The average skull thickness at each treatment field will be determined through post-processing the thin cut head computed tomography (CT) scan (without contrast).
• Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial
• Known acute or chronic types of porphyria
• Gastrointestinal disorder that negatively affects absorption
• Known active hepatitis B or C (Note: testing is not required)
• Known Human Immunodeficiency Virus (HIV) infection (Note: testing is not required)
• Unable to avoid photosensitising drugs (eg, St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, quinolones, and tetracyclines) for up to 2 weeks following 5-ALA administration
• Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g, clinically significant pulmonary disease, clinically significant psychiatric or neurological disorder, active or uncontrolled infection)
• Diagnosis of other invasive cancer (except basal cell carcinoma/squamous cell carcinoma of the skin) within the last 5 years; adequately treated carcinoma in situ is allowed
• Patient has a condition the investigator believes would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results or put the patient at undue risk

Sponsors & Collaborators

• Universität Münster: lead
• Alpheus Medical, Inc.: collaborator

Study Sites (1)

Department of Neurosurgery, University Hospital Münster

Münster, 48149, Germany

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Levulinic Acids; Keto Acids; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Walter Stummer, Univ.-Prof. Dr. med.

  Department of Neurosurgery, University Hospital Münster, Münster, Germany, 48149

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2024
• First Posted: October 30, 2024
• Study Start: January 27, 2025
• Primary Completion: February 9, 2026
• Study Completion: February 9, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)