Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma

Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma

Sponsors

Lead sponsor: Matthew Bucknor

Collaborator: Focused Ultrasound Foundation

Source University of California, San Francisco
Brief Summary

This is a single arm, single site, feasibility study of Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to promote immunotherapy responses in patients with undifferentiated pleomorphic sarcoma

Detailed Description

This study is a single arm, single site, feasibility study to evaluate the safety and efficacy of MRgFUS using the ExAblate 2100 System for the partial ablation of undifferentiated pleomorphic sarcomas. A total of 20 adult participants will be treated with MRgFUS through this study. A matched comparison group of archived samples from patients with UPS who have not received focused ultrasound will be used as a control group to further evaluate the secondary endpoints (stratified and matched for age, sex, and history of neoadjuvant chemotherapy). All patients enrolled will receive timely standard of care surgical resection

Primary Objective:

To evaluate the overall rate and severity of adverse events following pre-operative MRgFUS prior to surgical resection of undifferentiated pleomorphic sarcoma.

Secondary Objectives

1. To measure possible immune response effects related to MRgFUS by serial serological analysis with flow cytometry panels (T-cell, natural killer cell, myeloid panels).

2. To measure possible immune response effects related to MRgFUS by multiplex immunohistochemistry assays of resected tumor specimens (CD3, CD4, CD8, CD19, CD68, FOXP3, PD-1, PD-L1, CD45) as well as RNA sequencing.

3. To compare possible immune response effects in this group of patients receiving pre-operative MRgFUS prior to surgical resection of undifferentiated pleomorphic sarcoma to a comparison group of archived samples from patients who have had resection of UPS but did not have pre-operative focused ultrasound.

Overall Status Recruiting
Start Date January 23, 2020
Completion Date July 23, 2022
Primary Completion Date July 23, 2022
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of Any Device-Related Adverse Events Approximately 1-4 months
Secondary Outcome
Measure Time Frame
Percent change between baseline and post-treatment immune cell populations Approximately 1-4 months
Cytokine Concentrations Approximately 1-4 months
Identification of Immune Cell Populations in Sarcoma Tissue Approximately 1-4 months
Immunohistochemistry analyses Approximately 1-4 months
Enrollment 20
Condition
Intervention

Intervention type: Device

Intervention name: ExAblate 2000/2100 Magnetic Resonance-guided Focused Ultrasound (MRgFUS)

Description: The ExAblate 2100 MRgFUS system (InSightec, Inc., Dallas, Texas, USA) is a noninvasive thermal ablation device fully integrated with an MR imaging system and used for the ablation of soft tissue and bone.14-16 The ExAblate combines a focused ultrasound surgery (FUS) delivery system and a conventional diagnostic 3T Magnetic Resonance (MR) scanner. The ExAblate systems provide a real-time therapy planning algorithm, thermal dosimetry, and closed-loop therapy control. The ExAblate transducer device is an integrated component of the MR table

Arm group label: Magnetic Resonance-guided Focused Ultrasound (MRgFUS)

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 a biopsy-proven diagnosis of undifferentiated pleomorphic sarcoma.

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. 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. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 other than the current regimen.

3. History of interstitial lung disease or other active malignancy*

4. History of previous malignancies (except non-melanoma skin cancers)*

5. 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.

6. Subjects must have recovered from the effects of major surgery or significant trauma at least 14 days before the study procedure.

7. Subjects with an acute medical condition expected to hinder them from completing the study, unstable cardiovascular status, and severe cerebrovascular disease.

8. Treatment with any investigational agent within 28 days of the treatment procedure.

9. 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)

10. Unable to safely receive anesthesia/sedation for the treatment, or known intolerance or allergy to medications used for sedation/anesthesia.

11. Unable to verbally communicate with the investigator and staff.

12. Have received neoadjuvant radiotherapy or planning to receive neoadjuvant radiotherapy.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Matthew Bucknor, MD Principal Investigator University of California, San Francisco
Overall Contact

Last name: I-Wei Katherine Wu

Phone: (415) 353-9437

Email: [email protected]

Location
facility status contact contact_backup investigator University of California, San Francisco Maya Aslam, BA 415-514-8987 [email protected] Matthew Bucknor, MD Principal Investigator
Location Countries

United States

Verification Date

March 2020

Responsible Party

Responsible party type: Sponsor-Investigator

Investigator affiliation: University of California, San Francisco

Investigator full name: Matthew Bucknor

Investigator title: Assistant Professor in Residence

Keywords
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Magnetic Resonance-guided Focused Ultrasound (MRgFUS)

Arm group type: Experimental

Description: Pre-operative MRgFUS with the ExAblate 2000/2100 MRgFUS system 1-4 weeks prior to surgical resection of their tumor

Acronym HIFU-UPS
Patient Data Undecided
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: This study is a single arm, single site, feasibility study with a matched comparison group of archived samples for secondary endpoints

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov