Clinical trial NCT04123535: Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma
Official title: Focused Ultrasound to Promote Immune Responses for Undifferentiated Pleomorphic Sarcoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Undifferentiated Pleomorphic Sarcoma
Keywords: Focused Ultrasound
Sarcoma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Focused Ultrasound Foundation
name: InSightec-TxSonics
First posted: 2019-10-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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).

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. History of interstitial lung disease or other active malignancy (may confound immune response results).
3. History of previous malignancies (except non-melanoma skin cancers) (may confound immune response results).
4. 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.
5. Subjects must have recovered from the effects of major surgery or significant trauma at least 14 days before the study procedure.
6. Subjects with an acute medical condition expected to hinder them from completing the study, unstable cardiovascular status, and severe cerebrovascular disease.
7. Treatment with any investigational agent within 28 days of the treatment procedure.
8. 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)
9. Unable to safely receive anesthesia/sedation for the treatment, or known intolerance or allergy to medications used for sedation/anesthesia.
10. Unable to verbally communicate with the investigator and staff.
11. For Group 1 Patients (newly diagnosed disease) only: Have received neoadjuvant radiotherapy or planning to receive neoadjuvant radiotherapy.

Primary outcomes:
measure: Proportion of participants with reported Device-Related Adverse Events
timeFrame: Approximately 1-4 months
Secondary outcomes:
measure: Percent change between baseline and post-treatment T-cell populations
timeFrame: Approximately 1-4 months
measure: Percent change between baseline and post-treatment natural killer cell populations
timeFrame: Approximately 1-4 months
measure: Percent change between baseline and post-treatment myeloid cell populations
timeFrame: Approximately 1-4 months
measure: Percent change between baseline and post-treatment Cytokine Concentrations
timeFrame: Approximately 1-4 months
measure: Presence of Immune Cell Populations in Sarcoma Tissue
timeFrame: Approximately 1-4 months
measure: Immunohistochemistry analyses
timeFrame: Approximately 1-4 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Matthew Bucknor, MD
role: PRINCIPAL_INVESTIGATOR
References: