Focused Ultrasound for Sarcoma

(HIFU-UPS Trial)

Overseen By Louise Magat

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Matthew Bucknor

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Interstitial lung disease, Other malignancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1-4 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called ExAblate 2000/2100 Magnetic Resonance-guided Focused Ultrasound (MRgFUS) for undifferentiated pleomorphic sarcoma, a type of soft tissue cancer. It aims to determine if this treatment is safe and effective in partially destroying the cancer before surgery. Participants will receive the ultrasound treatment a few weeks before their tumors are surgically removed. This trial may suit individuals recently diagnosed with this type of sarcoma, who have a tumor between 2 and 20 cm, and whose tumor is visible on an MRI scan. As an unphased trial, this study offers a unique opportunity to explore a novel treatment approach before surgery.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids or other immunosuppressive medications at least 14 days before the treatment. If you are on these medications, you will need to stop them to participate.

What prior data suggests that this focused ultrasound technique is safe for treating sarcoma?

Research has shown that MRgFUS, or Magnetic Resonance-guided Focused Ultrasound, has been safely used in past studies. In one study involving 15 patients with extra-abdominal desmoid fibromatosis, MRgFUS reduced tumor size and alleviated pain. Patients tolerated the treatment well, and no serious side effects were reported, indicating likely safety.

Although the current trial is in the "Not Applicable" phase, meaning detailed safety data might not yet be available, previous use of this technology for similar conditions has demonstrated its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of Magnetic Resonance-guided Focused Ultrasound (MRgFUS) for treating sarcomas because it offers a non-invasive alternative to traditional surgery and chemotherapy. Unlike conventional treatments, which can involve significant recovery time and side effects, MRgFUS uses sound waves precisely targeted at the tumor, potentially reducing damage to surrounding healthy tissue. This technique can be performed with the ExAblate 2000/2100 system, allowing for real-time imaging and precise targeting, which might improve treatment accuracy and effectiveness. Additionally, MRgFUS may offer quicker recovery times and fewer side effects compared to existing options, making it a promising approach for patients with sarcomas.

What evidence suggests that the ExAblate 2000/2100 MRgFUS is effective for undifferentiated pleomorphic sarcoma?

Research has shown that MRgFUS (Magnetic Resonance-guided Focused Ultrasound), using systems like ExAblate 2100, effectively treats various types of tumors. This treatment uses sound waves to heat and destroy tumor cells without surgery. Studies have found it works well for tumors in areas like the breast and bones. As a noninvasive method, it does not involve cutting into the body. In this trial, all participants with sarcomas will receive pre-operative MRgFUS with the ExAblate 2000/2100 system to shrink tumors before surgery. Early results suggest it might also enhance the immune system's ability to fight cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Matthew Bucknor, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults over 18 with a new or suspected diagnosis of undifferentiated pleomorphic sarcoma, who are in good physical condition (ECOG score 0-1) and have tumors accessible to the ExAblate device. Tumors must be visible by MRI, at least 2 cm but no larger than 20 cm, and not too close to critical structures. Patients can't join if they've had recent immunosuppressants, other active cancers, unresolved treatment side effects (except hair loss/fatigue), major surgery/trauma within two weeks, unstable health conditions, contraindications for MRI including metal implants or severe claustrophobia.

Inclusion Criteria

I am fully active or can carry out light work.

I was recently diagnosed with undifferentiated pleomorphic sarcoma or have a lesion suspected to be this cancer.

My tumor is between 2 cm and 20 cm in size.

Exclusion Criteria

I do not have any severe health conditions that would prevent me from completing the study.

I am newly diagnosed and will have or had initial radiation therapy.

I haven't taken steroids or immunosuppressants in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Treatment Biopsy

Pre-procedure biopsy of the metastatic tumor target is conducted

2 weeks

1 visit (in-person)

Treatment

Participants receive MRgFUS treatment 1-4 weeks prior to surgical resection

1-4 weeks

1 visit (in-person)

Surgical Resection

Standard of care surgical resection is performed as clinically indicated

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-4 months

What Are the Treatments Tested in This Trial?

Interventions

• ExAblate 2000/2100 Magnetic Resonance-guided Focused Ultrasound (MRgFUS)

Trial Overview The trial is testing the safety and effectiveness of MRgFUS using the ExAblate System for partially ablating undifferentiated pleomorphic sarcomas. It's a single-site study where all participants receive this focused ultrasound treatment to see how well it works and what side effects occur.

How Is the Trial Designed?

Group I: Undifferentiated Pleomorphic Sarcoma (UPS) Experimental Treatment 1 Intervention

All enrolled participants will be scheduled to receive pre-operative MRgFUS with the ExAblate 2000/2100 MRgFUS system 1-4 weeks prior to surgical resection of their tumor or approximately 2 weeks after a pre-procedure biopsy of the metastatic tumor target depending on diagnosis at enrollment. For patients enrolled with metastatic disease, pre and post-MRgFUS biopsy samples will be obtained.

ExAblate 2000/2100 Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is already approved in United States for the following indications:

Approved in United States as ExAblate MRgFUS for:

• Uterine fibroids (leiomyomata)
• Palliation of pain associated with tumors metastatic to bone
• Medication refractory essential tremor
• Tremor-dominant Parkinson disease

Who Is Running the Clinical Trial?

Matthew Bucknor

Lead Sponsor

Trials

2

Recruited

80+

InSightec-TxSonics

Industry Sponsor

Trials

2

Recruited

70+

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

Published Research Related to This Trial

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 surgery (MRgFUS) is a noninvasive technique that has seen significant advancements and applications in treating various conditions, including musculoskeletal disorders.

The review highlights the limited existing literature on MRgFUS for musculoskeletal interventions while comparing it to a 3-year clinical experience, suggesting potential benefits and the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical role of HIFU in musculoskeletal interventions. Masciocchi, C., Conchiglia, A., Gregori, LM., et al.[2021]

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 first clinical experience with MRgFUS using the ExAblate 2100 system for non-invasive breast cancer showed promising results, with no severe adverse events reported in two patients.

Pathological examinations indicated that the treatment effectively induced tumor necrosis, suggesting that MRgFUS is a safe and feasible option for non-invasive breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases. Matsutani, A., Ide, Y., Miura, S., et al.[2020]

Magnetic Resonance-guided Focused Ultrasound (MRgFUS) effectively provided significant pain relief for patients with painful bone metastases, with all patients reporting improvement within 2 weeks after treatment.

The treatment was generally safe, with only minor adverse events such as non-specific leg pain and second-degree skin burns, while showing promising results in reducing tumor size and promoting new bone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pain palliation in patients with bone metastases using magnetic resonance-guided focused ultrasound with conformal bone system: a preliminary report. Joo, B., Park, MS., Lee, SH., et al.[2018]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04123535

Focused Ultrasound to Promote Immune Responses for ... This study is a single site, single-arm, feasibility study to evaluate the safety and efficacy of MRgFUS using the ExAblate 2100 System for the partial ablation ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04123535

Focused Ultrasound to Promote Immune Responses for ... This study is a single site, single-arm, feasibility study to evaluate the safety and efficacy of MRgFUS using the ExAblate 2100 System.

3. withpower.com withpower.com/trial/phase-histiocytoma-malignant-fibrous-2020-57f2f

Focused Ultrasound for Sarcoma (HIFU-UPS Trial) Research shows that MRgFUS, using systems like ExAblate 2100, has been effective in treating various tumors, including breast and bone tumors, by noninvasively ...

4. smartpatients.com smartpatients.com/trials/NCT04123535

Focused Ultrasound to Promote Immune Responses for ... This study is a single site, single-arm, feasibility study to evaluate the safety and efficacy of MRgFUS using the ExAblate 2100 System for the partial ablation ...

5. journals.lww.com journals.lww.com/topicsinmri/fulltext/2018/02000/magnetic_resonance_imaging_guided_high_intensity.10.aspx

Topics in Magnetic Resonance Imaging Their results using the ExAblate 2000 device showed that MR-HIFU ablation ... sarcoma patients over the past 3 decades: surveillance epidemiology and end results ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5097700/

Magnetic Resonance-Guided Focused Ultrasound Treatment ... Conclusions. MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.