SuizenjiFeasibility Study of Suizenji, in Patients With Unresectable Pancreatic Ductal Adenocarcinoma (SUNRISE-II)

1. Signed an Institutional Review Board (IRB) approved informed consent document.
2. Men and women ≥ 18 years of age.
3. Histologically or cytologically diagnosed PDAC.
4. Newly diagnosed unresectable\*, locally advanced or metastatic disease. (\* defined as not "Resectable" and not "borderline resectable" based on "Criteria Defining Resectability at Diagnosis" in NCCN Guideline 2024)
5. Primary tumor accessible to HIFU treatment and visualized on transabdominal ultrasonography.
6. Primary tumor site must be a measurable lesion according to RECIST version 1.1 at baseline.
7. ECOG Performance Status (ECOG-PS) of 0 - 1.
8. Life expectancy ≥ 3 months.
9. Adequate organ function defined by:

• Neutrophil count: ≥ 1,500/mm3
• Platelet count: ≥ 50,000/mm3
• Hemoglobin: ≥ 8.0 g/dl
• Cr: ≤ 1.7 mg/dl
• AST, ALT: ≤ 3 x upper limit of normal
• T-Bil: ≤ 2 x upper limit of normal

Exclusion Criteria:

1. Subjects with any cancers other than PDAC who are on active treatment.
2. Subjects who had any prior chemotherapy or interventions for PDAC.
3. Obstructive jaundice (except for subjects who have a bile duct stent placed for obstructive jaundice prior to initiation of HIFU treatment).
4. Tumor embolization in the veins surrounding the pancreas.
5. Cysts outside of primary pancreatic tumor which may obstruct the HIFU sonication pathway. However, if the cyst is completely surrounded by pancreatic tumor, the subject can be included.
6. Subjects with > 50% reduction in caliber of the principal hepatic artery and occlusion of the portal vein seen on preoperative screening CT or MRI scan.
7. Allergy to contrast agents (except when manageable by prophylactic steroid).
8. Subjects having a cardiac pacemaker.
9. Congestive heart failure, symptomatic coronary artery disease, arrhythmia poorly controlled by drugs, history of myocardial infarction or unstable angina within the past 6 months.
10. Subjects with peritoneal dissemination.
11. Active infections requiring systemic treatment.
12. Pregnancy or women of childbearing potential not willing to follow the birth control as described in the informed consent and/or who are breastfeeding.
13. Received unapproved or investigational drug or device within 30 days of the subject's study start date.
14. The judgment of the investigator would make the subject inappropriate for entry into the study.