Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma

Brief Title

Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma

Official Title

Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma

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.
    


Study Type

Interventional


Primary Outcome

Incidence of Any Device-Related Adverse Events

Secondary Outcome

 Percent change between baseline and post-treatment immune cell populations

Condition

Undifferentiated Pleomorphic Sarcoma

Intervention

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

Study Arms / Comparison Groups

 Magnetic Resonance-guided Focused Ultrasound (MRgFUS)
Description:  Pre-operative MRgFUS with the ExAblate 2000/2100 MRgFUS system 1-4 weeks prior to surgical resection of their tumor

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Device

Estimated Enrollment

20

Start Date

January 23, 2020

Completion Date

July 23, 2022

Primary Completion Date

July 23, 2022

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

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Matthew Bucknor, MD, 877-827-3222, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04123535

Organization ID

19653

Secondary IDs

NCI-2019-06737

Responsible Party

Sponsor-Investigator

Study Sponsor

Matthew Bucknor

Collaborators

 Focused Ultrasound Foundation

Study Sponsor

Matthew Bucknor, MD, Principal Investigator, University of California, San Francisco


Verification Date

August 2020