Undifferentiated Pleomorphic Sarcoma
Conditions
Keywords
Focused Ultrasound, Sarcoma
Brief summary
This study is a single site, single-arm, feasibility study to evaluate the safety and efficacy of MRgFUS using the ExAblate 2100 System for the partial ablation of undifferentiated pleomorphic sarcomas.
Detailed description
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, as clinically indicated. For patients enrolled with metastatic disease pre- and post-MRgFUS biopsy samples will be obtained PRIMARY OBJECTIVE: I. To evaluate the overall rate and severity of adverse events following MRgFUS of newly diagnosed or metastatic undifferentiated pleomorphic sarcoma. SECONDARY OBJECTIVES: I. To measure possible immune response effects related to MRgFUS by serial serological analysis with flow cytometry panels (T-cell, natural killer cell, myeloid panels). II. 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. III. To compare possible immune response effects in patients receiving MRgFUS prior to either surgical resection or follow-up biopsy of undifferentiated pleomorphic sarcoma to either 1) a comparison group of archived samples from patients who have had resection of UPS but did not have pre-operative focused ultrasound (for patients with newly diagnosed local disease or 2) individual pre-MRgFUS biopsy analyses.
Interventions
DEVICEExAblate 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
Sponsors
Matthew Bucknor
Focused Ultrasound Foundation
InSightec-TxSonics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with reported Device-Related Adverse Events | Approximately 1-4 months | Proportion of participants with device-related adverse events will be determined by evaluating the incidence and severity of any device-related complications from the treatment day visit through the time of surgery or last post-treatment point. Patients will be followed for any reported adverse events following MRgFUS, per the Common Terminology Criteria for Adverse Events version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent change between baseline and post-treatment T-cell populations | 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 populations. Percent change between baseline and post-treatment samples will be calculated and displayed as a table |
| Percent change between baseline and post-treatment natural killer cell populations | 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 natural killer cell populations. Percent change between baseline and post-treatment samples will be calculated and displayed as a table |
| Percent change between baseline and post-treatment myeloid cell populations | 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 myeloid cell populations. Percent change between baseline and post-treatment samples will be calculated and displayed as a table |
| Percent change between baseline and post-treatment Cytokine Concentrations | Approximately 1-4 months | 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 |
| Presence of Immune Cell Populations in Sarcoma Tissue | Approximately 1-4 months | The detectable presence of various 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. |
| Immunohistochemistry analyses | Approximately 1-4 months | Immunohistochemistry analyses in patients with newly diagnosed local UPS 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. Nanostring digital spatial profiling may also be used for tissue analysis |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMatthew Bucknor, MD
University of California, San Francisco
Outcome results
None listed