Magnetic Resonance Guided High Intensity Focused Ultrasound in Advanced Pancreatic Adenocarcinoma Treatment

Study Overview
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Brief Summary
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The primary purpose of this protocol is to assess the ExAblate 2100 MR guided high intensity focused ultrasound device as an intervention for treatment of advanced stage pancreatic adenocarcinoma.

Detailed Description
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Primary Objective: The primary endpoints for this study will be 1) feasibility of ablation and 2) safety of ablation. Secondary Objective: 1.)Pain reduction after ablation. 2.) Evidence of inflammation at ablation site based on histology, or in blood after ablation

Official Title
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A Phase I Study of Magnetic Resonance Guided High Intensity Focused Ultrasound for Treatment of Advanced Pancreatic Adenocarcinoma

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Device: ExAblate 2100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥ 18 years of age Patients willing to sign a written informed consent document Patients with unresectable, locally advanced or metastatic pancreatic adenocarcinoma Patients with upper abdominal pain rating at least 4 out of 10 in severity on BPI Tumor must be visualized on CT or MRI, obtained within 30 days of enrollment Tumor must be accessible to the ExAblate MRgFUS device Life expectancy ≥ 3 months, as determined by oncologist and documented in chart ECOG performance status of 0, 1, or 2 INR < 1.6, platelet count > 50,000 microL Serum urate, calcium, potassium, phosphate, creatinine < 1.5x upper limit of normal Patients can receive general anesthesia, as determined by anesthesiologist Exclusion Criteria: Previous pancreatic surgery Patients with contraindication for MR imaging such as implanted metallic devices that are not MRI-safe, size limitations, claustrophobia, etc. Patients with known intolerance or allergy to MR contrast agent (gadolinium chelates) including advanced kidney disease (GFR <30 mL/min/1.73 m2) or on dialysis Pregnant and nursing patients will be excluded from the study because of a contraindication to administering MRI contrast agents to these patients Patients unable to receive general anesthesia Target is: NOT visible by non-contrast MRI, OR NOT accessible to ExAblate device Individuals who are not able or willing to tolerate the required prolonged stationary position during treatment (can be up to 6 hrs of total table time) Patients with acute medical condition (e.g. pneumonia, sepsis) that is expected to hinder them from completing this study Patients with unstable cardiac status including: Unstable angina pectoris on medication Patients with documented myocardial infarction within six months of protocol entry Congestive heart failure requiring medication (other than diuretic) Patients on anti-arrhythmic drugs Patients with severe hypertension (diastolic BP > 100 on medication) Patients with severe hematologic, neurologic, or other uncontrolled disease (e.g. platelets < 50,000/microL, INR > 1.5) Patients who are taking anti-thrombotic medication Severe cerebrovascular disease (multiple CVAs or CVA within 6 months)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRgFUS Treatment<br>The pancreatic tumor will be ablated with magnetic resonance guided focused ultrasound (MRgFUS). | Device: ExAblate 2100<br>* A non-invasive thermal ablation device fully integrated with an MR imaging system<br>* Other names: InSightec ExAblate 2100 MRgHIFU system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure acceptable ablation percentage | Feasibility of ablation, as measured by the number of patients with acceptable ablation percentage. Acceptable ablation percentage is defined as ≥50% of the targeted volume appearing ablated on post-treatment imaging. Ablation will be deemed feasible if at least seven of the ten patients have an acceptable ablation percentage | Immediately after MRgFUS treatment | 
| Total frequency and severity of adverse events | Safety of ablation, as measured by the total frequency and severity of adverse events. Adverse events will be categorized and grade for severity according to the Common Terminology Criteria for Adverse Events, Version 5.0. Ablation will be deemed safe if there are no treatment-related serious adverse events, and no more than five moderate or mild treatment-related adverse events, among the ten patients during follow up. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess Pain Response assessed by the Brief Pain Inventory (BPI) | Reduction in pain level, as measured by: a. a decline in pain score after one week of at least 2 points, or a pain score < 4 out of 10, as assessed by the Brief Pain Inventory. Ablation will be deemed pain reducing if at least five of the ten patients have pain reduction. | Baseline, 1 week, and monthly for 24 months following treatment | 
| Assess Pain Response assessed by morphine equivalent daily dose (MEDD) | Reduction in pain level will be measured by a decline after one week in morphine equivalent daily dose (MEDD) of 25%. Ablation will be deemed pain reducing if at least five of the ten patients have pain reduction. | Baseline, 1 week, and monthly for 24 months following treatment | 
| Evidence of ablation-induced inflammation | Evidence of ablation-induced inflammation, defined as post-ablation increases in histologic and/or blood measures of inflammation markers, as measured by either: an increase in tumor infiltrating CD8+ T cells a decrease in immune suppressive cells (Tregs, macrophages) in the tumor an increase in immune activation signatures (including interferon gamma) in the tumor as measured by RNAseq a change in immune profile in the circulating immune cells (PBMCs) to reflect an activated immune response (e.g. activated T or B cells, reduction in immune suppressive cells or cytokines) Ablation will be deemed inflammation-inducing if at least five of the ten patients show at least a 50% increase in inflammation on at least 2 of the 4 markers | 1week |