Using focused ultrasound to enhance immune responses in undifferentiated pleomorphic sarcoma

Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma

This study is testing if a special ultrasound treatment can safely help boost the immune response in adults with undifferentiated pleomorphic sarcoma while they also receive standard surgery.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Drugs / interventions: chemotherapy, doxorubicin
• Locations: 1 site (San Francisco, California)
• Trial ID: NCT04123535 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of Magnetic Resonance-guided Focused Ultrasound (MRgFUS) for partially ablating undifferentiated pleomorphic sarcomas in adult patients. A total of 20 participants will receive MRgFUS treatment, with a matched comparison group of archived samples from patients who did not undergo this treatment. The study aims to assess adverse events and measure immune response effects through various analyses, including serological tests and immunohistochemistry. All enrolled patients will also receive standard surgical resection as clinically indicated.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with biopsy-proven undifferentiated pleomorphic sarcoma or highly suspicious metastatic lesions.

Not a fit: Patients with tumors not accessible to the ExAblate device or those with critical structures nearby may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve immune responses in patients with undifferentiated pleomorphic sarcoma, potentially enhancing treatment outcomes.

How similar studies have performed: While focused ultrasound is a novel approach in this context, similar studies have shown promise in enhancing immune responses in other cancer types.

Eligibility criteria

Inclusion Criteria:

1. Men and women \>= 18 years old.
2. Eastern Cooperative Oncology Group (ECOG) performance-status score of 0-1.
3. Subjects must have either 1) a biopsy-proven new diagnosis of undifferentiated pleomorphic sarcoma (UPS) (within the last 6 months) or 2) a lesion highly suspicious for metastatic UPS based on CT or MRI imaging (within the last 6 months).
4. Target tumor \>= 2 cm in maximum diameter and \<= 20 cm in maximum diameter.
5. Target tumor accessible to the ExAblate device in the soft tissues of the chest, abdomen, pelvis, or upper or lower extremities.
6. Target tumor must be \> 1 cm from any critical structure. Critical structures are defined as skin, major nerve/vascular bundles, nerve roots, any solid organ, and any portion of the bowel.
7. Target tumor must be clearly visible by non-contrast magnetic resonance imaging (MRI)
8. For patients with newly diagnosed, not previously treated UPS, tumor must be deemed to be surgically resectable by tumor board documentation or surgeon's note.
9. To clarify, patient's being treated with institutional standard neoadjuvant chemotherapy may be included in this study if all other inclusion/exclusion criteria are met.

   * Note: There has never been a prospective study comparing patients receiving chemotherapy to those not receiving chemotherapy in the neoadjuvant setting for soft tissue sarcoma. Our local institutional standard is to treat patients with neoadjuvant chemotherapy prior to surgical resection when tumors are \> 5 cm in maximal dimension and within deep muscular compartments. Our institutional standard is to treat patients with doxorubicin plus ifosfamide for younger patients (typically \<50 years old) and gemcitabine plus taxotere for older patients (typically \>= 50 years old).

Exclusion Criteria:

1. Subjects requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of Magnetic Resonance-guided Focused Ultrasound (MRgFUS) treatment date.
2. History of interstitial lung disease or other active malignancy (may confound immune response results).
3. History of previous malignancies (except non-melanoma skin cancers) (may confound immune response results).
4. All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline.
5. Subjects must have recovered from the effects of major surgery or significant trauma at least 14 days before the study procedure.
6. Subjects with an acute medical condition expected to hinder them from completing the study, unstable cardiovascular status, and severe cerebrovascular disease.
7. Treatment with any investigational agent within 28 days of the treatment procedure.
8. Any absolute contraindications for study magnetic resonance imaging (MRI) per standard University of California, San Francisco (UCSF) departmental MRI safety guidance (https://radiology.ucsf.edu/patient-care/patient-safety/mri) and additionally:

   * Metal in other parts of body that will cause safety issues
   * Claustrophobia
   * Weight \> 400 pounds (lb) or 181.4 kilograms (kg).
   * Pregnancy
   * Known intolerance or allergy to magnetic resonance (MR) contrast agent (gadolinium chelates)
9. Unable to safely receive anesthesia/sedation for the treatment, or known intolerance or allergy to medications used for sedation/anesthesia.
10. Unable to verbally communicate with the investigator and staff.
11. For Group 1 Patients (newly diagnosed disease) only: Have received neoadjuvant radiotherapy or planning to receive neoadjuvant radiotherapy.

Where this trial is running

San Francisco, California

• University of California, San Francisco — San Francisco, California, United States (Recruiting)

Study contacts

• Principal investigator: Matthew Bucknor, MD — University of California, San Francisco
• Study coordinator: Louise Magat

Conditions Undifferentiated Pleomorphic Sarcoma; Focused Ultrasound; Sarcoma