Study to Evaluate 5-ALA Combined With CV01 Delivery of Ultrasound in Recurrent High Grade Glioma

NCT05362409 | Completed Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: CV01-101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

A Phase 1 Multi-center clinical Trial Evaluating the Safety and Tolerability of 5-aminolevulinic Acid (5-ALA) Combined With CV01 Delivery of Ultrasound for Sonodynamic Therapy (SDT) in Patients With recurrent High Grade Glioma (HGG).

Conditions

High Grade Glioma

Keywords

Cancer; Brain Cancer; Sonodynamic; Glioma; High Grade Glioma (HGG); Sonodynamic therapy (SDT); Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (Safety and Tolerability)

  Safety and tolerability as determined by the incidence of adverse events (AEs), including severe AEs and serious AEs (SAEs)

  12 Months

• To determine the Maximum Tolerable Duration (MTDu)

  The MTDu is defined as the highest duration at which fewer than 1/3 of patients experience a Duration limited toxicity

  12 Months

Secondary Outcomes (4)

• Assessment of Overall response rate (ORR)

  12 Months

• Assessment of Duration of Response (DoR)

  12 Months

• Assessment of Overall survival (OS)

  12 Months

• Assessment of Progression free survival (PFS)

  12 Months

Study Arms (1)

5-ALA with CV01

EXPERIMENTAL

5-aminolevulinic acid \[5-ALA\] with CV01-delivered ultrasound

Drug: 5 Aminolevulinic Acid; Device: CV01-delivered ultrasound

Interventions

5 Aminolevulinic Acid DRUG

5-aminolevulinic acid \[5-ALA\] administered orally 20 mg/kg every 4 weeks

Also known as: 5-ALA, Gleolan

5-ALA with CV01

CV01-delivered ultrasound DEVICE

CV01-delivered ultrasound every 4 weeks

5-ALA with CV01

Eligibility Criteria

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

You may qualify if:

• Patient must provide informed consent, stating understanding of the procedures and investigational nature of the study treatment, and willingness to comply with study requirements
• ≥ 18 years of age
• WHO performance status of ≤ 2 at screening
• Part A: Previous histopathologically confirmed diagnosis of high-grade glioma and radiographic evidence of recurrence after prior therapy with radiotherapy. Eligible histologies include (according to WHO classification 2021):
• Astrocytoma, WHO grade 3 and 4 (including subtypes)
• Oligodendroglioma WHO grade 3 (including subtypes)
• Parts B and C: Previous histopathologically confirmed diagnosis of glioblastoma and radiographic evidence of recurrence after prior therapy with radiotherapy. While Part A may include patients with any type of HGG and any number of recurrences, Parts B and C are restricted to patients with glioblastoma experiencing first recurrence.
• Unifocal or multifocal tumor confined to the supratentorial compartment
• Interval since last anti-cancer therapy relative to first 5-ALA treatment, as detailed below
• End of radiotherapy \>12 weeks (including skin-directed radiation for skin cancer),
• Last cytotoxic chemotherapy (4 weeks, if prior nitrosureas 6 weeks).
• Last biological therapy, i. If bevacizumab ≥ 6 weeks ii. If other monoclonal antibody, e.g., immune checkpoint inhibitor \> 3 weeks iii. If tyrosine kinase inhibitor or other small molecule \> 2 weeks
• Any other investigational agent(s) ≥ 30 days or 5 half-lives, whichever is longer
• Photodynamic therapy for skin cancer or actinic keratoses ≥ 12 weeks
• Any toxicity attributable to prior anti-cancer therapy must be resolved to the patient's baseline level or ≤ Grade 1 (except alopecia).

You may not qualify if:

• Primary infratentorial or brainstem tumors
• Primary spinal cord tumors
• Bihemispheric disease (enhancing or non-enhancing) or tumors that involve the bilateral corpus callosum
• Women who are pregnant or breastfeeding
• Inability to undergo MRI or receive gadolinium (Gd)-based contrast agents
• Hypersensitivity to 5-ALA or porphyrins
• Average skull thickness at the treatment field \> 10 mm as assessed by Alpheus Medical.
• 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 by Alpheus Medical through post-processing the thin cut head computed tomography (CT) (without contrast). The patient's CT scan must be provided to Alpheus Medical for evaluation as part of the Screening and Enrollment process.
• Patients who have clinically significant edema requiring urgent intervention (e.g., surgery, initiation of steroids, escalating doses of steroids).
• Patients with progressive and rapid clinical deterioration that, in the opinion of the investigator, is likely to worsen during the first cycle of treatment or in the peri-operative interval (in the surgical cohort)
• Cumulative prior RT dose \> 64 Gy
• 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)

Sponsors & Collaborators

• Alpheus Medical, Inc.: lead

Study Sites (3)

Washington University School of Medicine in St.Louis

St Louis, Missouri, 63110, United States

Location

Dent Neurosciences Research Center

Amherst, New York, 14226, United States

Location

Northwell

Lake Success, New York, 11042, United States

Location

MeSH Terms

Conditions

Glioma; Neoplasms; Brain Neoplasms; Glioblastoma

Interventions

Aminolevulinic Acid

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma

Intervention Hierarchy (Ancestors)

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

Study Design

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

Model Details: Part A will include cohorts at escalating duration of sonication. Parts B and C will include the recommended duration as determined in Part A.

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: May 5, 2022
• Study Start: June 29, 2022
• Primary Completion: December 3, 2024
• Study Completion: February 3, 2025
• Last Updated: June 19, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)