What is the mechanism of action of this treatment?

Sonodynamic Therapy (SDT) with MRgFUS and Intravenous Aminolevulinic Acid HCl (ALA) works by using focused ultrasound to activate ALA, a photosensitizer that selectively accumulates in tumor cells. Upon activation, ALA produces reactive oxygen species that induce tumor cell apoptosis and necrosis, sparing surrounding healthy tissue. This targeted approach is crucial for brain tumor patients as it minimizes damage to critical brain structures, potentially preserving neurological function and improving quality of life. Other common treatments include surgical resection, radiation therapy, and chemotherapy, which aim to remove or kill tumor cells but often affect healthy brain tissue as well.

What side effects are associated with this type of intervention?

Treatments similar to Sonodynamic Therapy (SDT) with MRgFUS and Intravenous Aminolevulinic Acid HCl (ALA) can cause a range of side effects. Photodynamic therapy (PDT) with ALA often results in skin photosensitivity, pain at the treatment site, and local inflammation. Focused ultrasound therapy may lead to headache, scalp pain, and transient neurological symptoms. Therefore, SDT may combine these side effects, potentially leading to enhanced local tissue reactions due to the synergistic effects of ultrasound and photosensitizer activation.

What prior FDA approvals exist?

The FDA has approved several treatments for brain tumors, including chemotherapeutic agents like temozolomide and targeted therapies such as bevacizumab. While there is no direct mention of FDA-approved treatments that use a combination of focused ultrasound and photosensitizers like ALA for brain tumors, photodynamic therapy (PDT) using photosensitizers has been explored in other contexts. PDT involves the use of light-activated drugs to selectively destroy cancer cells, which is conceptually similar to the mechanism of SDT. However, specific FDA approvals for brain tumor treatments using this exact method are not detailed in the provided context.

What other types of research exist?

Promising novel alternatives to SDT with MRgFUS and ALA for brain tumor patients include: 1) Intraoperative MRI-guided resection, which enhances the extent of tumor removal and improves outcomes. 2) Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA), which helps in better visualization and resection of malignant gliomas. 3) Antisense oligonucleotide therapy, such as Tofersen for SOD1 ALS, which is being explored for its potential in treating neurodegenerative diseases and may have applications in brain tumors. 4) Emerging systemic therapies like lenvatinib for progressive, metastatic tumors, which have shown efficacy in clinical trials.

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Device

Sonodynamic Therapy for Brain Cancer

Phase < 1

Recruiting

Led By Nader Sanai, MD

Research Sponsored by Nader Sanai

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 14 days is required between last chemotherapy dose and Day 1 (provided the patient did not receive radiotherapy).

Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant has had a hysterectomy.

Must not have

Diagnosis of porphyria

Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment that uses sound waves and a special drug to target brain cancer cells. The drug is given in a way that makes the cancer cells more sensitive to the sound waves. The treatment aims to help patients whose brain cancer has returned after previous treatments.

Who is the study for?

This trial is for adults over 18 with high-grade gliomas (brain tumors) that have recurred after standard therapy. Participants must be in relatively good health, not pregnant or breastfeeding, and willing to use effective contraception. They should not have serious bleeding disorders, heart conditions, certain infections, or an inability to undergo MRI.

What is being tested?

The study tests sonodynamic therapy using MR-guided focused ultrasound (MRgFUS) combined with a drug called ALA on patients with recurrent brain tumors. It's a first-in-human study assessing different energy doses of this treatment for safety and effectiveness.

What are the potential side effects?

Potential side effects are not detailed but may include typical reactions to intravenous drugs like ALA such as allergic reactions or photosensitivity. The MRgFUS procedure might cause discomfort or risks associated with exposure to focused ultrasound.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have recovered from chemotherapy side effects, except for possible hair loss or mild nerve pain.

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I am not pregnant or I have had a hysterectomy.

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I finished my radiotherapy at least 14 days ago and have recovered from its immediate effects.

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I had surgery for a serious brain tumor and it has gotten worse after standard treatment.

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My cancer recurrence was confirmed by a biopsy or a special MRI scan.

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I am 18 years old or older.

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I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with porphyria.

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I do not have any active infections requiring IV antibiotics or known viral infections like HIV or active hepatitis B or C.

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I am currently experiencing a severe worsening of my COPD.

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I do not have a bleeding disorder or blood clotting problem.

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I have a serious heart rhythm problem that isn't well-controlled.

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I had a major heart attack in the last 6 months.

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I have a serious blood vessel condition.

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I am not taking medications that increase sensitivity to light.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Biological changes associated with the sonodynamic therapy

Radiographic evidence of tumor physiological imaging changes associated with SDT in recurrent HGG patients (Arm E)

Secondary study objectives

Best Overall Response (BOR)

Overall Survival

Performance of MRgFUS

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Arm E Optimal energy and ALA doseExperimental Treatment1 Intervention

In Arm E patients will receive treatment at the optimal energy and ALA dose determined form prior Arms.

Group II: Arm D MRgFUS aloneExperimental Treatment1 Intervention

In Arm D, MRgFUS treatment alone will be given at the optimal energy determined from previous Arms.

Group III: Arm C ALA Dose-escalationExperimental Treatment1 Intervention

In Arm C, the MRgFUS power/energy dose will be fixed based on Arm A MTD/OBD, with the SONALA-001 dose escalation.

Group IV: Arm B Time-escalationExperimental Treatment1 Intervention

In Arm B, the time-escalation cohort, the SONALA-001 and power/energy dose combination will be fixed. Participants will be enrolled into two time cohorts (2 days and 6 days post-SDT).

Group V: Arm A Energy Dose-escalationExperimental Treatment1 Intervention

In Arm A, the dose-escalation cohort, there will be 3 cohorts of ascending MRgFUS power/energy dose combinations with a fixed SONALA-001 dose and fixed surgical time. Arm A will determine the power/energy dose combination for Arm B.

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Sonodynamic Therapy (SDT) with MRgFUS and Intravenous Aminolevulinic Acid HCl (ALA) works by using focused ultrasound to activate ALA, a photosensitizer that selectively accumulates in tumor cells. Upon activation, ALA produces reactive oxygen species that induce tumor cell apoptosis and necrosis, sparing surrounding healthy tissue. This targeted approach is crucial for brain tumor patients as it minimizes damage to critical brain structures, potentially preserving neurological function and improving quality of life. Other common treatments include surgical resection, radiation therapy, and chemotherapy, which aim to remove or kill tumor cells but often affect healthy brain tissue as well.

Imaging-guided focused ultrasound-induced thermal and sonodynamic effects of nanosonosensitizers for synergistic enhancement of glioblastoma therapy.Study of the mechanism of sonodynamic therapy in a rat glioma model.

Find a Location

Who is running the clinical trial?

Nader SanaiLead Sponsor

8 Previous Clinical Trials

298 Total Patients Enrolled

Barrow Neurological InstituteOTHER

26 Previous Clinical Trials

7,005 Total Patients Enrolled

Ivy Brain Tumor CenterOTHER

11 Previous Clinical Trials

809 Total Patients Enrolled

SonALAsense, Inc.Industry Sponsor

3 Previous Clinical Trials

423 Total Patients Enrolled

InSightecIndustry Sponsor

91 Previous Clinical Trials

3,768 Total Patients Enrolled

Nader Sanai, MDPrincipal Investigator - St. Joseph's Hospital and Medical Center, Phoenix

Barrow Neurological Institute at St. Joseph's, Chandler Regional Medical Center, Select Specialty Hospital-Phoenix, St. Joseph's Hospital & Medical Center

University Of California (Medical School)

University Ca Sf School Of Medicine (Residency)

13 Previous Clinical Trials

989 Total Patients Enrolled