Summary

for people ages 18 years and up (full criteria)
at San Francisco, California
study started
estimated completion
Matthew Bucknor, MD

Description

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

Details

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.

Keywords

Undifferentiated Pleomorphic Sarcoma Focused Ultrasound Sarcoma Histiocytoma, Malignant Fibrous ExAblate 2000/2100 Magnetic Resonance-guided Focused Ultrasound (MRgFUS) Magnetic Resonance-guided Focused Ultrasound (MRgFUS)

Eligibility

You can join if…

Open to people ages 18 years and up

  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.

  1. Target tumor must be clearly visible by non-contrast magnetic resonance imaging (MRI)
  2. Tumor must be deemed to be surgically resectable by tumor board documentation or surgeon's note.
  3. To clarify, patient's being treated with institutional standard neoadjuvant chemotherapy may be included in this study if all other inclusion/

You CAN'T join if...

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:
  10. Metal in other parts of body that will cause safety issues
  11. Claustrophobia
  12. Weight > 400 pounds (lb) or 181.4 kilograms (kg).
  13. Pregnancy
  14. Known intolerance or allergy to magnetic resonance (MR) contrast agent (gadolinium chelates)
  15. . Unable to safely receive anesthesia/sedation for the treatment, or known intolerance or allergy to medications used for sedation/anesthesia.
  16. . Unable to verbally communicate with the investigator and staff.
  17. . Have received neoadjuvant radiotherapy or planning to receive neoadjuvant radiotherapy.

Location

  • University of California, San Francisco not yet accepting patients
    San Francisco California 94143 United States

Lead Scientist

  • Matthew Bucknor, MD
    Matthew Bucknor, MD, is an Associate Professor in Residence in the Musculoskeletal Imaging subspecialty section, and the Inaugural Associate Chair for Wellbeing and Professional Climate in the UCSF Department of Radiology and Biomedical Imaging.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
Matthew Bucknor
ID
NCT04123535
Study Type
Interventional
Last Updated