5-ALA + Ultrasound for Glioblastoma

Recruiting at 1 trial location

Overseen By Ann-Marie VP, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alpheus Medical, Inc.

Must be taking: Temozolomide

Must not be taking: Phototoxic drugs

Disqualifiers: Infratentorial tumors, Bihemispheric disease, Gliosarcoma, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 hours for 5-ALA administration prior to 40 minutes of LIDU SDT, followed by standard of care Temozolomide

103 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat glioblastoma, a type of brain cancer, using an experimental drug called 5-ALA with a special ultrasound device (Low Intensity Diffuse Ultrasound Sonodynamic Therapy System). The goal is to determine if this combination can effectively target and kill cancer cells after surgery and chemoradiation. Participants will receive either the active treatment or a placebo (inactive version) while continuing their standard cancer medication, Temozolomide. The trial seeks individuals newly diagnosed with glioblastoma who have completed surgery and initial treatments without disease progression. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

What prior data suggests that this investigational device and drug combination is safe for treating glioblastoma?

Research has shown that using 5-ALA (a type of acid) with low-intensity ultrasound appears safe. In animal studies, this combination did not harm healthy brain tissue, suggesting it targets only tumor cells and spares surrounding areas.

Further research supports this finding. A clinical trial with humans found that most participants tolerated this method well, experiencing no serious side effects. Studies also suggest that it remains safe even with repeated use.

Although this treatment is still under study, current evidence indicates it is safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for glioblastoma, which typically involve surgery, radiation, and chemotherapy with drugs like temozolomide (TMZ), the combination of 5-ALA and low intensity diffuse ultrasound sonodynamic therapy (LIDU SDT) offers a novel approach. This treatment is unique because it leverages 5-ALA, a compound that accumulates in tumor cells, making them more susceptible to the effects of ultrasound. The ultrasound then activates the 5-ALA, potentially leading to more targeted tumor destruction without harming surrounding healthy tissue. Researchers are excited about this potential to precisely target glioblastoma cells, which could improve outcomes and reduce side effects compared to conventional therapies.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

This trial will compare the use of 5-ALA with ultrasound to a placebo for treating glioblastoma. Research shows that 5-ALA, a drug that makes cancer cells light up, combined with ultrasound, might help treat glioblastoma, a type of brain cancer. This treatment uses sound waves to activate 5-ALA, targeting and destroying cancer cells. Early studies have shown positive results, such as killing cancer cells without harming healthy ones. Initial tests in animals, like dogs with brain tumors, have also demonstrated the method's safety. The goal is to enhance standard treatment by adding this new approach. Participants in this trial will receive either the experimental 5-ALA and ultrasound treatment or a placebo, both followed by standard care with Temozolomide. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with newly diagnosed glioblastoma who've completed surgery and chemoradiation without disease progression. They must have good organ function, no severe side effects from previous treatments (except hair loss or low lymphocytes), and not be pregnant or breastfeeding. Women of childbearing potential must use effective contraception.

Inclusion Criteria

8. Adequate bone marrow and organ function, defined by the following laboratory values: A. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3 B. Platelet count ≥ 50,000 cells/mm3 C. Hemoglobin (Hgb) ≥ 8 g/dl D. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN) E. Total bilirubin ≤ 3 x ULN (unless gilbert's syndrome, then patients may be eligible if total serum bilirubin is ≤ 5.0 x ULN or direct bilirubin is ≤ 3 x ULN) F. Creatinine clearance (CrCl) as estimated by Cockcroft-Gault equation of ≥ 50 ml/min

My blood clotting tests are within normal range or not significantly high.

I understand the study's procedures and risks, and agree to follow its requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 5-ALA with LIDU SDT or a placebo with sham SDT, along with standard of care Temozolomide

6-8 hours for 5-ALA administration prior to 40 minutes of LIDU SDT, followed by standard of care Temozolomide

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Low Intensity Diffuse Ultrasound Sonodynamic Therapy System
• Temozolomide

Trial Overview

The study tests a new treatment combining an investigational drug (5-ALA) with a non-invasive ultrasound device (LIDU SDT) against placebo plus sham ultrasound in patients receiving standard oral Temozolomide therapy. Participants are randomly assigned to either the active treatment group or the control group, with neither knowing which one they're in.

How Is the Trial Designed?

Group I: Arm A: (experimental arm) Experimental Treatment 1 Intervention

* 5-ALA HCl (5-amino-levulenic acid) for oral solution (20 mg/kg) p.o. 6-8 hours prior to LIDU SDT * LIDU SDT System (low intensity diffuse ultrasound sonodynamic therapy), for 40 minutes followed by standard of care TMZ * SOC TMZ to be started Day 2 (+/-1 day) per the approved PI

Group II: Arm B: (placebo arm) Placebo Group 1 Intervention

* Placebo oral solution (matched to 20 mg/kg) p.o. 6-8 hours prior to Sham SDT * Sham SDT for 40 mimnutes followed by standard of care TMZ * SOC TMZ to be started Day 2 (+/-1 day) per the approved PI

Who Is Running the Clinical Trial?

Alpheus Medical, Inc.

Lead Sponsor

Trials

2

Recruited

40+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12113153/

Sonodynamic Therapy Using 5-Aminolevulinic Acid for ...

This review provides an insight into the use of focused and diffuse ultrasound in the treatment of GBM using 5-ALA-SDT, its mechanism of action and immune ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07225621

Study Details | NCT07225621 | Adjuvant Temozolomide ...

This study is evaluating an experimental treatment for glioblastoma that uses an investigational drug (5-ALA) combined with a non-invasive ...

3.

academic.oup.com

academic.oup.com/neuro-oncology/article-abstract/26/Supplement_8/viii319/7890425

Neuro-Oncology | Oxford Academic

Although preliminary, these results affirm the safety of 5-ALA-mediated SDT in canine glioma patients. A multi-center, First-In-Human trial in ...

4.

prnewswire.com

prnewswire.com/news-releases/alpheus-medical-publishes-promising-early-clinical-results-of-sonodynamic-therapy-for-the-treatment-of-newly-diagnosed-glioblastomas-302384164.html

Alpheus Medical Publishes Promising Early Clinical ...

The study reported no adverse effects with an immediate positive imaging and histopathological response indicating cancer cell death, with no impact on healthy ...

5.

link.springer.com

link.springer.com/article/10.1007/s11060-025-04957-7

Sonodynamic therapy with a single neoadjuvant, diffuse ...

The objective of this case study is to report on the first applications of 5-aminolevulinic acid (5-ALA) in combination with low-intensity, non- ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06665724

Study Details | NCT06665724 | Clinical Trial Evaluating ...

This trial is designed to evaluate safety and explore possible efficacy of 5-aminolevulinic acid hydrochloride (5-ALA HCl, Gliolan®) with CV01 delivery of ...

7.

nature.com

nature.com/articles/s41416-025-03325-6

Efficacy and safety of low- and high-intensity focused ...

These outcomes underscore LIFU's safety for repeated applications, even in complex cases involving implantable devices or combination therapies.

8.

fusfoundation.org

fusfoundation.org/posts/sonodynamic-therapy-studies-show-safety-provide-review-for-this-novel-glioma-treatment/

Sonodynamic Therapy Studies Show Safety, Provide ...

Researchers recently published a preclinical safety study and a review of the technology as used in gliomas. A first-in-human clinical trial ...