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Trial record 1 of 1 for:    NCT04123535
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Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma (HIFU-UPS)

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ClinicalTrials.gov Identifier: NCT04123535
Recruitment Status : Recruiting
First Posted : October 11, 2019
Last Update Posted : March 24, 2020
Sponsor:
Collaborator:
Focused Ultrasound Foundation
Information provided by (Responsible Party):
Matthew Bucknor, 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

Condition or disease Intervention/treatment Phase
Undifferentiated Pleomorphic Sarcoma Device: ExAblate 2000/2100 Magnetic Resonance-guided Focused Ultrasound (MRgFUS) Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma
Actual Study Start Date : January 23, 2020
Estimated Primary Completion Date : July 23, 2022
Estimated Study Completion Date : July 23, 2022


Arm Intervention/treatment
Experimental: Magnetic Resonance-guided Focused Ultrasound (MRgFUS)
Pre-operative MRgFUS with the ExAblate 2000/2100 MRgFUS system 1-4 weeks prior to surgical resection of their tumor
Device: ExAblate 2000/2100 Magnetic Resonance-guided Focused Ultrasound (MRgFUS)
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
Other Names:
  • ExAblate 2000/2100
  • MRgFUS




Primary Outcome Measures :
  1. Incidence of Any Device-Related Adverse Events [ Time Frame: Approximately 1-4 months ]
    Patients will be followed for any reported adverse events following Magnetic Resonance-guided Focused Ultrasound (MRgFUS), using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and evaluated on incidence and severity to create a safety profile. Device-related Adverse Events (AEs) will be will be summarized as percentages, with computed confidence intervals.


Secondary Outcome Measures :
  1. Percent change between baseline and post-treatment immune cell populations [ Time Frame: Approximately 1-4 months ]
    Blood samples obtained at 1 week prior to MRgFUS and at 1 week post MRgFUS will be sent to the University of California, San Francisco (UCSF) Cancer Immunotherapy Lab. Flow cytometry panels will be performed to evaluate T-cell, natural killer cell, and myeloid cell populations. Cytokine concentrations will also be measured. Percent change between baseline and post-treatment samples will be calculated and displayed as a table

  2. Cytokine Concentrations [ Time Frame: Approximately 1-4 months ]
    Serological analyses: blood samples obtained at 1 week prior to MRgFUS and at 1 week post MRgFUS. Cytokine concentrations will also be measured. Percent change between baseline and post-treatment samples will be calculated

  3. Identification of Immune Cell Populations in Sarcoma Tissue [ Time Frame: Approximately 1-4 months ]
    Immune populations in tumor specimens, including populations of CD3, CD4, CD8, CD19, CD68, FOXP3, PD-1, PD-L1, and CD45 positive cells will be determined. RNA sequencing will also be performed. Identification if displayed as a table

  4. Immunohistochemistry analyses [ Time Frame: Approximately 1-4 months ]
    Immunohistochemistry analyses will be compared to an archived matched group of patients (matched for age, sex, and history of neoadjuvant chemotherapy) who had resection of UPS without pre-operative MRgFUS.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04123535


Contacts
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Contact: I-Wei Katherine Wu (415) 353-9437 katherine.wu@ucsf.edu
Contact: Matthew Bucknor, MD cancertrials@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Maya Aslam, BA    415-514-8987    Maya.Aslam@ucsf.edu   
Contact: Matthew Bucknor, MD    877-827-3222    cancertrials@ucsf.edu   
Principal Investigator: Matthew Bucknor, MD         
Sponsors and Collaborators
Matthew Bucknor
Focused Ultrasound Foundation
Investigators
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Principal Investigator: Matthew Bucknor, MD University of California, San Francisco

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Responsible Party: Matthew Bucknor, Assistant Professor in Residence, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04123535    
Other Study ID Numbers: 19653
NCI-2019-06737 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
First Posted: October 11, 2019    Key Record Dates
Last Update Posted: March 24, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Matthew Bucknor, University of California, San Francisco:
Focused Ultrasound
Sarcoma
Additional relevant MeSH terms:
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Sarcoma
Histiocytoma, Malignant Fibrous
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Histiocytoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue