This is a single arm phase II study. All patients will receive 3 cycles of the treatment of nab-paclitaxel (Days 1, 8 and 15), gemcitabine (Days 1, 8 and 15), and TTFields (worn every day for at least 18 hours). Following the initial 3 cycles of gemcitabine/nab-paclitaxel/TTFields treatment, patients will undergo restaging by CT or MRI. Patients with stable disease or better will undergo surgery for resection within 8 weeks following completion of initial chemotherapy although enrolling sites are encouraged to perform resection within 4 weeks of Cycle 3 D15 of therapy. If resection yields R0 or R1, patients will begin an additional 3 cycles of gemcitabine/nab-paclitaxel/TTFields treatment within 8 weeks of surgery. Based on available literature, it is expected that a percentage of patients will not undergo resection either due to disease progression or due to toxicities/ complications of the neoadjuvant segment of therapy. These patients will be included in the evaluable patients for both co-primary endpoints as well as the secondary endpoints including ORR, adverse events, and OS.

Inclusion Criteria:

-Written informed consent and HIPAA authorization for release of personal health information.

NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

• Male or non-pregnant, non-lactating female age ≥ 18 years at the time of consent.

• Karnofsky Performance Status (KPS) of ≥70% within 7 days prior to registration.

• Histological or cytological evidence of pancreatic adenocarcinoma.

• Patients must have resectable primary tumor per NCCN definitions version 2.2021 based on contrast-enhanced CT or MRI (CT or MRI without contrast as part of PET/CT or PET/MRI is NOT acceptable; CT or MRI with contrast as part of PET/CT or PET/MRI is acceptable) of the chest, abdomen, and pelvis, where resectable is defined as all of the following:

  • No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (and, if present, replaced right hepatic artery).
  • No involvement, or < 180° interface between tumor and vessel wall, of the portal vein and/or superior mesenteric vein; and patent portal vein/splenic vein confluence.
  • No evidence of metastatic disease. NOTE: To minimize ineligible patients, an institutional checklist, identical to the one used by the central radiologist at the end of the study, will be mandated for completion by the enrolling site investigator or radiologist. The 6-point checklist will include visible pancreatic mass; measurable disease; absence of arterial interface; venous interface of less than or equal to 180°; patent portal-splenic confluence; and absence of metastatic disease, including lymphadenopathy outside the surgical basin.

• Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to registration.

• Patients must not have received prior surgery, radiation therapy, chemotherapy, targeted therapy, or any investigational therapy for pancreatic cancer.

• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration.

  • Hematological

    • Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
    • Hemoglobin (Hgb) ≥ 8.0 g/dL
    • Platelets ≥100,000/mm3

  • Renal

    ---Calculated creatinine clearance ≥ 30 cc/min using the Cockcroft-Gault formula

  • Hepatic

    • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 3 × ULN
    • Alanine aminotransferase (ALT) ≤ 3 × ULN

• Females of childbearing potential must have a negative pregnancy test (serum or urine) within 3 days prior to registration. See the protocol for definition of childbearing potential.

• Females of childbearing potential must be willing to abstain from vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study, and for 6 months after the last dose of study drug(s). Males must be willing to abstain from vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study, and for 3 months after the last dose of study drug(s). See also the protocol (contraception).

• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.

• Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.

Exclusion Criteria:

• Evidence of distant metastasis
• Patients with an electrical implantable device in the torso. Examples of electrical implanted medical devices include spinal cord stimulators, vagus nerve stimulators, pacemakers, and defibrillators.
• History of significant uncontrolled cardiovascular disease. Significant cardiac disease includes second/third degree heart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but ordinary activity results in fatigue, palpitation or dyspnea).
• History of arrhythmia that is symptomatic or requires treatment. Patients with atrial fibrillation or flutter controlled by medication are not excluded from participation in the trial -Known allergy to medical adhesives or conductive hydrogel (gel used on electrocardiogram (ECG) stickers or transcutaneous electrical nerve stimulation (TENS) electrodes).
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial.
• Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol: (e.g., chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.)
• No prior malignancy is allowed except for adequately treated basal (or squamous cell) skin cancer, in situ cervical cancer or other cancer for which the patient has been disease and treatment-free for two years.
• Patient is unwilling or unable to comply with study procedures.