Sonodynamic Therapy for Brain Cancer

Overseen By Phase 0 Navigator

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nader Sanai

Must not be taking: Phototoxic substances

Disqualifiers: Infections, Stroke, Cardiac issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, there is a required 14-day period without chemotherapy or radiotherapy before starting the trial. Also, you cannot use other potentially phototoxic substances during the study.

Is MR-Guided Focused Ultrasound (MRgFUS) generally safe for humans?

MR-Guided Focused Ultrasound (MRgFUS) has been studied for safety in treating various conditions like breast cancer, bone tumors, and pain from bone metastases, showing it is generally safe for these uses. ^{1 2 3 4 5}

How is the Sonodynamic Therapy for Brain Cancer treatment different from other treatments?

This treatment is unique because it uses MR-guided focused ultrasound (MRgFUS) to noninvasively target brain tumors, enhancing the delivery of drugs like SONALA-001 (ALA) by temporarily disrupting the blood-brain barrier, which is a major challenge in treating brain cancer. ^{2 3 6 7 8}

What data supports the effectiveness of the treatment Sonodynamic Therapy for Brain Cancer using MR-Guided Focused Ultrasound device (MRgFUS)?

MR-Guided Focused Ultrasound (MRgFUS) has been shown to be effective in treating various conditions like uterine fibroids, breast cancer, and bone metastases by using focused sound waves to heat and destroy targeted tissue. It is also being explored for brain disorders, offering a noninvasive alternative to traditional surgery. ^{2 3 6 8 9}

Who Is on the Research Team?

Nader Sanai, MD

Principal Investigator

St. Joseph's Hospital and Medical Center, Phoenix

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I can understand and am willing to sign the consent form myself or have someone legally authorized to do so.

My blood tests show my organs and bone marrow are working well.

Exclusion Criteria

I have been diagnosed with porphyria.

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

I am currently experiencing a severe worsening of my COPD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous ALA followed by sonodynamic therapy (SDT) with MRgFUS

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including radiographic and biological assessments

4-14 days

Multiple visits (in-person)

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• MR-Guided Focused Ultrasound device (MRgFUS)
• SONALA-001(ALA) and MR-Guided Focused Ultrasound device (MRgFUS)

Trial Overview 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.

How Is the Trial Designed?

Group I: Arm E Optimal energy and ALA dose Experimental Treatment 1 Intervention

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

Group II: Arm D MRgFUS alone Experimental Treatment 1 Intervention

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

Group III: Arm C ALA Dose-escalation Experimental Treatment 1 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-escalation Experimental Treatment 1 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-escalation Experimental Treatment 1 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.

MR-Guided Focused Ultrasound device (MRgFUS) is already approved in United States for the following indications:

Approved in United States as MRgFUS for:

• Research use in clinical trials for recurrent high-grade glioma

Who Is Running the Clinical Trial?

Nader Sanai

Lead Sponsor

Trials

11

Recruited

440+

Barrow Neurological Institute

Collaborator

Trials

27

Recruited

7,100+

Ivy Brain Tumor Center

Collaborator

Trials

12

Recruited

910+

SonALAsense, Inc.

Industry Sponsor

Trials

4

Recruited

450+

InSightec

Industry Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Published Research Related to This Trial

Magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive technique that can precisely target and treat brain disorders by creating thermal lesions and disrupting the blood-brain barrier, which is a significant advancement in neurotherapeutics.

MRgFUS has been successfully used in various clinical applications, including treating bone metastases and uterine fibroids, and is being explored as a safer alternative to traditional neurosurgery for a range of brain-related conditions, supported by studies from small animal models to large clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. Lipsman, N., Mainprize, TG., Schwartz, ML., et al.[2021]

A novel method using craniectomy and a high-frequency transducer significantly improved the accuracy of targeting small brain structures in rodents, achieving a 133% increase in precision compared to previous methods.

This approach allows for effective noninvasive lesioning of deep brain areas, which is crucial for studying neurological disorders in chronic disease models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain. Cornelssen, C., Payne, A., Parker, D., et al.[2023]

In a study involving 13 patients with painful bone metastases, MRgFUS was found to be a safe procedure, with no severe adverse events reported during the 6-month follow-up period.

The treatment showed initial efficacy, as 10 out of 12 patients experienced significant pain relief and reduced need for pain medication after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases--preliminary clinical experience. Catane, R., Beck, A., Inbar, Y., et al.[2022]

High frequency focused ultrasound (MRgFUS) is a promising non-invasive therapy for treating tumors, showing effectiveness and safety in initial clinical experiences with uterine fibroids, breast cancer, and fibroadenomas.

The use of MRI guidance enhances the precision of focused ultrasound treatments, making it a strong candidate for future applications in other tumor types, including liver and brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Magnetic resonance tomography guided focussed ultrasound surgery (MRgFUS) in tumor therapy--a new noninvasive therapy option]. Hengst, SA., Ehrenstein, T., Herzog, H., et al.[2018]

In a study involving 30 women with breast cancer, MRgFUS treatment resulted in an impressive average of 96.9% tumor necrosis, indicating its high effectiveness in ablating breast carcinomas.

The procedure was well tolerated with minimal adverse effects, especially when performed under local anesthesia, suggesting it could be a safe noninvasive alternative to traditional surgical methods like lumpectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. Furusawa, H., Namba, K., Thomsen, S., et al.[2022]

Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective incisionless treatment for centrally located brain lesions in adolescents and young adults, with no complications reported in a study of 5 patients aged 15-22.

The procedure successfully achieved thermoablation in 4 out of 5 cases, leading to improvements in symptoms such as seizure control, demonstrating its potential therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. Tierney, TS., Alavian, KN., Altman, N., et al.[2022]

In a study involving 24 patients, MRgFUS demonstrated significant efficacy in treating benign bone tumors, achieving complete ablation with minimal adverse effects, and effectively reducing pain in patients with metastatic bone disease.

The treatment resulted in 100% necrosis of ablated primary malignant tumors, indicating its potential as a safe and noninvasive option for managing both primary and metastatic bone tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance guided focused ultrasound for treatment of bone tumors. Singh, VA., Shah, SU., Yasin, NF., et al.[2018]

The novel TRANS-FUSIMO Treatment System (TTS) successfully quantifies key parameters for liver tumor ablation using Magnetic Resonance Guided Focused Ultrasound (MRgFUS), achieving a maximum deviation of only 0.16 seconds from planned sonication duration, which is crucial for safe and effective treatment.

The study demonstrated that the sonication process is consistent across different operators, indicating reliability in the system's performance, which is essential for clinical applications and quality assurance in medical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation. Mihcin, S., Karakitsios, I., Le, N., et al.[2018]

Magnetic resonance-guided focused ultrasound (MRgFUS) has been shown to effectively and safely disrupt the blood-brain barrier (BBB), enhancing the delivery of various chemotherapeutic agents into brain tumors, as evidenced by preclinical studies and initial clinical trials.

The use of MRgFUS in glioma patients has demonstrated improved penetration of drugs like gadolinium across the BBB, indicating its potential to improve treatment outcomes, although further research is needed to fully understand drug distribution and effects on tumor growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Strategies for Brain Tumor Therapy. Bunevicius, A., McDannold, NJ., Golby, AJ.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Intracranial applications of magnetic resonance-guided focused ultrasound. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain. [2023]

3. England pubmed.ncbi.nlm.nih.gov

MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases--preliminary clinical experience. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

[Magnetic resonance tomography guided focussed ultrasound surgery (MRgFUS) in tumor therapy--a new noninvasive therapy option]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound surgery of breast cancer: reliability and effectiveness. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Magnetic resonance guided focused ultrasound for treatment of bone tumors. [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

Methodology on quantification of sonication duration for safe application of MR guided focused ultrasound for liver tumour ablation. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Strategies for Brain Tumor Therapy. [2022]