ExAblate for Brain Cancer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must not be taking: Anticoagulants, NSAIDs, Statins, Immunosuppressants

Disqualifiers: Brain edema, Hemodynamic instability, Diabetes, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

A Study to Evaluate the Safety and Feasibility of Transcranial MRI-Guided Focused Ultrasound Surgery in the Treatment of Brain Tumors

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on anti-coagulant therapy or medications that increase the risk of bleeding. You can continue taking corticosteroids to prevent or treat brain swelling.

What data supports the effectiveness of the ExAblate Transcranial System treatment for brain cancer?

The ExAblate Transcranial System uses focused ultrasound, which is mentioned as a method to temporarily disrupt the blood-brain barrier, potentially improving the delivery of cancer treatments to the brain. This approach is part of ongoing research to enhance the effectiveness of therapies for brain tumors. ^{1 2 3 4 5}

What safety data exists for ExAblate Transcranial System or similar treatments for brain conditions?

The safety of stereotactic radiosurgery (a precise form of radiation therapy) combined with other treatments like chemotherapy and immunotherapy for brain conditions has been studied, showing it is generally safe without significant skin issues, bleeding, or severe radiation damage. ^{6 7 8 9 10}

How is the ExAblate Transcranial System treatment different from other brain cancer treatments?

The ExAblate Transcranial System is unique because it uses focused ultrasound to target brain tumors, potentially bypassing the blood-brain barrier that often limits the effectiveness of traditional chemotherapy drugs. ^{3 11 12 13 14}

Eligibility Criteria

This trial is for adults aged 18-75 with brain tumors smaller than 2.5 cm in diameter or metastatic brain cancer that's worsened after radiotherapy. It's an option when surgery isn't suitable and the tumor is well-defined on MRI scans, located more than 2.5 cm from the skull's inner table, and patients can handle steroids before/after treatment.

Inclusion Criteria

Able and willing to give informed consent.

My glioma has returned or worsened despite standard treatments, and surgery or more radiation isn't recommended.

Tumor(s) are clearly defined on pre-therapy contrast enhanced MRI scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MRI-guided focused ultrasound surgery using the ExAblate Transcranial Device

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the ExAblate treatment

4 weeks

Treatment Details

Interventions

• ExAblate Transcranial System

Trial Overview The study tests the safety and feasibility of using ExAblate Transcranial System, a non-invasive MRI-guided focused ultrasound surgery method to treat brain tumors without traditional surgical procedures.

Participant Groups

Group I: ExAblate Transcranial Device Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

InSightec

Lead Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Findings from Research

Brain and spinal tumors, affecting 1 in 1000 people by age 25, have a high mortality rate of 30-40%, but most patients survive with significant long-term disabilities due to brain injuries acquired before and after treatment.

Current drug delivery techniques are being explored to improve the effectiveness of treatments for brain tumors by enhancing drug penetration across the blood-brain barrier or bypassing it altogether, which could lead to better patient outcomes and the potential re-evaluation of previously ineffective drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. Rahman, R., Janowski, M., Killick-Cole, CL., et al.[2023]

In a study of 17 patients aged 2 to 25 years with unfavorable brain tumors, a combined treatment of chemotherapy and radiotherapy led to a median overall survival of 36 months, with 9 patients still alive at a median follow-up of 25 months.

While the treatment showed promise with 4 complete remissions and 2 partial remissions, it also resulted in severe toxicity, including one therapy-related death, highlighting the need for careful management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults. Urban, C., Benesch, M., Pakisch, B., et al.[2019]

In a study of 260 patients treated for brain and skull base tumors with photon and particle therapies, no unexpected severe toxicities were reported, indicating a favorable safety profile for these treatments.

The use of particle therapy, particularly protons and carbon ions, shows promise in potentially reducing the risk of secondary malignancies and improving neurocognitive outcomes, although longer follow-up is needed to confirm these benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. Combs, SE., Kessel, K., Habermehl, D., et al.[2016]

A review of 77 studies involving 6384 patients found that stereotactic radiosurgery (SRS) combined with systemic therapies (like chemotherapy and immunotherapy) is safe, showing no significant increase in skin toxicities, bleeding, or radiation necrosis.

The median SRS dose was 20 Gy, and the findings support the continuation of systemic treatments alongside SRS for patients with brain metastases, indicating that this combination does not adversely affect patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. Borius, PY., Régis, J., Carpentier, A., et al.[2021]

A review of 166 phase III randomized clinical trials published between 2011 and 2013 revealed frequent misreporting of adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0), indicating a significant issue in adherence to established guidelines.

Inappropriate grading of toxicities was common, with serious conditions like febrile neutropenia often graded too low, and less severe conditions like alopecia graded too high, which could mislead clinicians and affect treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and misuse of common terminology criteria for adverse events in cancer clinical trials. Zhang, S., Liang, F., Tannock, I.[2018]

The study demonstrates the successful use of a novel implantable convection-enhanced delivery (CED) system for carboplatin in a patient with recurrent glioblastoma, showing precise catheter placement and well-tolerated drug infusions.

Follow-up MRI results indicated a significant reduction in tumor volume from 42.6 ml to 24.6 ml after treatment, suggesting that CED of carboplatin may improve clinical outcomes for glioblastoma patients by effectively bypassing the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma. Barua, NU., Hopkins, K., Woolley, M., et al.[2022]

References

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

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

Pediatric Cancer. [2021]

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

Optimizing the Delivery of Antineoplastic Therapies to the Central Nervous System. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. [2023]

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

Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults. [2019]

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

Survival was Significantly Better with Surgical/Medical/Radiation Co-interventions in a Single-Institution Practice Audit of Frameless Stereotactic Radiosurgery. [2020]

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

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base. [2016]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of radiosurgery concurrent with systemic therapy (chemotherapy, targeted therapy, and/or immunotherapy) in brain metastases: a systematic review. [2021]

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

Competing Risk Analysis of Neurologic versus Nonneurologic Death in Patients Undergoing Radiosurgical Salvage After Whole-Brain Radiation Therapy Failure: Who Actually Dies of Their Brain Metastases? [2023]

10. England pubmed.ncbi.nlm.nih.gov

Use and misuse of common terminology criteria for adverse events in cancer clinical trials. [2018]

11. France pubmed.ncbi.nlm.nih.gov

[Pharmacologic bases of chemotherapy of brain tumors in children]. [2009]

12. England pubmed.ncbi.nlm.nih.gov

A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma. [2022]

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

Phosphodiesterase type 5 inhibitors increase Herceptin transport and treatment efficacy in mouse metastatic brain tumor models. [2021]

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

Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier disruption in malignant brain tumors: the Sherbrooke experience. [2022]