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)

A Phase 1 Single Center 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

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.

Study Overview

• Status: Completed
• Conditions: Anaplastic Astrocytoma (AA); Anaplastic Oligodendroglioma (AO); Glioblastoma (GBM)
• Intervention / Treatment: Drug: 5-Aminolevulinic acid Hydrochloride (Gliolan®); Device: CV01

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. WHO Performance Status of 0-2
3. 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.
4. Planned debulking or cytoreductive surgery

5. The following laboratory values at study entry

   1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
   2. Platelet count ≥ 100,000 cells/mm3
   3. Hemoglobin (Hgb) > 10g/dL
   4. AST and ALT ≤ 2.5 x Upper Limit of Normal (ULN)
   5. Total bilirubin ≤ 1.5 x ULN

   6. Creatine clearance (CrCL) as estimated by Cockcroft-Gault equation of

      ≥ 40 mL/min

   7. Blood clotting within acceptable limits according to investigator
6. 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®.
7. Ability to understand and provide informed consent

Exclusion Criteria:

1. Infra-tentorial tumors
2. Patients who have clinically significant edema or tumor mass effect requiring urgent intervention (e.g., surgery, initiation of steroids, escalating doses of steroids)
3. Women who are pregnant or breastfeeding
4. Inability to undergo MRI or receive gadolinium (Gd)
5. Hypersensitivity to 5-ALA or porphyrins
6. 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).
7. Hemorrhagic or ischemic stroke (including transient ischemic attacks) and central nervous system bleeding in the preceding 6 months that are not related to glioma biopsy. History of prior intratumoral bleeding is not an exclusion criterion; however, all patient's navigation CTs will be reviewed for the presence of fresh blood.
8. Participation in another interventional clinical trial during this trial or within 4 weeks before entry into this trial
9. Known acute or chronic types of porphyria
10. Gastrointestinal disorder that negatively affects absorption
11. Known active hepatitis B or C (Note: testing is not required)
12. Known Human Immunodeficiency Virus (HIV) infection (Note: testing is not required)
13. 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
14. 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)
15. 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
16. 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
17. Patients who are dependent on the sponsor, investigator or trial site
18. Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sonodynamic Therapy (SDT); 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®); Patients will receive 5-Aminolevulinic acid hydrochloride via oral administration (20 mg/kg) 6-8 hours before CV01 treatment.; Device: CV01; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histopathological efficacy	Anti-tumor activity assessed by Number of cells / mm³ with antibodies against IBA1 and Number of cells / mm³ with antibodies against Caspase III	Biopsies will be collected during standard surgery.
Radiological changes	Radiological changes (MRI) of Tumor volume, Volume of FLAIR hyperintensity, Volume of cyctotoxic edema, Relative cerebral blood volume and Leakage	Changes from visit 1 (< 8 days before sonodynamic therapy) to visit 3 (2 to 5 days after sonodynamic therapy)

Collaborators and Investigators

• Sponsor: Universität Münster
• Collaborators: Alpheus Medical, Inc.
• Investigators: Principal Investigator: Walter Stummer, Univ.-Prof. Dr. med., Department of Neurosurgery, University Hospital Münster, Münster, Germany, 48149

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2025
• Primary Completion (Actual): February 9, 2026
• Study Completion (Actual): February 9, 2026

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: October 29, 2024
• First Posted (Actual): October 30, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: newly diagnosed high-grade glioma; sonodynamic therapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Astrocytoma; Oligodendroglioma; Amino Acids, Peptides, and Proteins; Organic Chemicals; Carboxylic Acids; Amino Acids; Keto Acids; Levulinic Acids; Aminolevulinic Acid
• Other Study ID Numbers: WWU22_0032; 2023-509238-20-00 (Ctis); UTN: U1111-1296-1261 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No