Endoscopic Ultrasound Radiofrequency Ablation and Immunotherapy Pembrolizumab for Locally Advanced Unresectable and Metastatic Pancreatic Duct Adenocarcinoma

Eligibility Criteria

• * Is willing and able to comply with the protocol for the duration of the study,including undergoing treatment and scheduled visits and examinations, including follow-up
• * Biopsy-proven locally advanced unresectable or metastatic PDAC
• 1. Patients who have undergone prior resection will be excluded unless there is recurrent pancreatic tumor that is amenable to EUS-RFA.
• 2. If biliary metal stent is placed, during procedure of EUS-RFA, indwelling biliary metal stent will be removed during initial EUS-RFA and then replaced with plastic stent.
• * Mental capacity to provide informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• * Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
• * At least one measurable metastatic lesion on axial imaging per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
• * No prior systemic therapy, including chemotherapy or chemoradiation is permitted with the following exceptions:
• 1. Prior adjuvant therapy (including chemotherapy and/or radiotherapy) for pancreatic adenocarcinoma is permitted if neoadjuvant or adjuvant therapy was completed at least 3 months prior to study enrollment. Prior adjuvant therapy may include mFFX, NALIRIFOX, or GA.
• 2. If started on first-line treatment for mPDAC elsewhere (i.e., not at our study site), eligible participants can have undergone 3 months of chemotherapy with stable disease before study entry. Note: Imaging done outside the site will need to be reviewed for a 2nd opinion to confirm stable disease.
• * Absolute neutrophil count (ANC) ≥1 x 109/L
• * Platelet count ≥75 x 109/L
• * Total serum bilirubin \<2× upper limit of normal (ULN) unless secondary to Gilbert's Syndrome
• * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤3× ULN, or ≤5× ULN in cases of documented liver involvement
• * Serum creatinine clearance must be ≥30 mL/minute either measured or calculated using a standard Cockcroft and Gault formula
• * Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed at least 4 weeks before immunotherapy.
• * No telephone number and permanent street address
• * Pregnant or breastfeeding patients; or is a male or female patient of reproductive potential who is not willing to employ effective birth control from time of screening to 90 days after the last dose
• * Inmates or prisoners
• * Unable to provide informed consent
• * Resectable, borderline resectable PDAC.
• * Known history of central nervous system (CNS) metastases
• * Has a history of another primary malignancy. Patients having the following are still eligible:
• 1. No active stage 4 cancer
• 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• 3. Adequately treated carcinoma in situ without evidence of disease
• * Known low or absent dihydropyrimidine dehydrogenase (DPD) activity
• * Use of strong inhibitors or inducers of Cytochrome P450 3A (CYP3A), CYP2C8 and UGT1A1
• * History or evidence of clinically significant or uncontrolled cardiovascular, CNS,and/or other systemic disease that in the investigator's opinion would preclude participation in the study or compromise the patient's ability to give informed consent
• * History of HIV or active tuberculosis (TB) (PPD response without active TB is allowed)
• * Underlying medical conditions that, in the Investigator's opinion, will make the administration of pembrolizumab hazardous (e.g., interstitial lung disease, active infections requiring antibiotics, recent hospitalization with unresolved symptoms)
• * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• * Any active autoimmune disease or a documented history of autoimmune disease or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy
• 1. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
• 2. Physiologic doses of corticosteroids (≤10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤3 days) may be permitted.
• 3. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• 4. Patients having any chronic skin condition that does not require systemic therapy
• 5. Patients without active disease in the last 5 years (allowed only after consultation with the study physician)
• 6. Patients with celiac disease controlled by diet alone
• * Is currently using or previously used immunosuppressive medication within 14 days before the first dose of pembrolizumab. The following medications are exceptions to this criterion:
• 1. intranasal, inhaled, topical steroid, or local steroid injections (e.g., intra articular injection)
• 2. Systemic corticosteroids at physiologic doses not to exceed 10mg/day of prednisone or its equivalent
• 3. steroids as premedication for hypersensitivity reactions (e.g., computer tomography \[CT\] scan premedication)