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

• ClinicalTrials.gov Identifier: NCT04298242
• Recruitment Status: Active, not recruiting
• First Posted: March 6, 2020
• Last Update Posted: October 26, 2022
• Sponsor: Stanford University
• Information provided by (Responsible Party): Stanford University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Adenocarcinoma	Device: ExAblate 2100	Not Applicable

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Device Feasibility
• Official Title: A Phase I Study of Magnetic Resonance Guided High Intensity Focused Ultrasound for Treatment of Advanced Pancreatic Adenocarcinoma
• Actual Study Start Date: November 22, 2020
• Estimated Primary Completion Date: November 2022
• Estimated Study Completion Date: November 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Measure acceptable ablation percentage [ Time Frame: Immediately after MRgFUS treatment ]
   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
2. Total frequency and severity of adverse events [ Time Frame: 24 months ]
   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.

Secondary Outcome Measures :

1. Assess Pain Response assessed by the Brief Pain Inventory (BPI) [ Time Frame: Baseline, 1 week, and monthly for 24 months following treatment ]

   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.

2. Assess Pain Response assessed by morphine equivalent daily dose (MEDD) [ Time Frame: Baseline, 1 week, and monthly for 24 months following treatment ]
   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.
3. Evidence of ablation-induced inflammation [ Time Frame: 1week ]

   Evidence of ablation-induced inflammation, defined as post-ablation increases in histologic and/or blood measures of inflammation markers, as measured by either:

   1. an increase in tumor infiltrating CD8+ T cells
   2. a decrease in immune suppressive cells (Tregs, macrophages) in the tumor
   3. an increase in immune activation signatures (including interferon gamma) in the tumor as measured by RNAseq
   4. 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

Eligibility Criteria

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

Criteria

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:

  1. NOT visible by non-contrast MRI, OR
  2. 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:

  1. Unstable angina pectoris on medication
  2. Patients with documented myocardial infarction within six months of protocol entry
  3. Congestive heart failure requiring medication (other than diuretic)
  4. Patients on anti-arrhythmic drugs
  5. Patients with severe hypertension (diastolic BP > 100 on medication)
  6. 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)

Contacts and Locations

Locations

United States, California

Stanford Cancer Center

Stanford, California, United States, 94304

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Pejman Ghanouni; Stanford University

More Information

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT04298242
• Other Study ID Numbers: IRB-52567; PANC0034 ( Other Identifier: OnCore ); NCI-2020-13809 ( Other Identifier: CTRP )
• First Posted: March 6, 2020
• Last Update Posted: October 26, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms