Adaptive Approach to Neoadjuvant Therapy to Maximize Resection Rates for Pancreatic Adenocarcinoma

Inclusion Criteria:

* Diagnosis of pancreatic carcinoma or adenocarcinoma confirmed by tissue. Histologies other than carcinoma or adenocarcinoma are not allowed.
* Resectable or borderline resectable primary tumor, evaluated on a baseline contrast-enhanced CT or MRI scan (CT Chest/Abdomen/Pelvis with contrast is preferred; if MRI used at baseline, then follow up with MRI as well), and defined using Intergroup criteria:

  * Tumor vessel wall interface 0-360 for portal and superior mesenteric veins.
  * Tumor vessel wall interface \<180 for celiac, common hepatic, and superior mesenteric arteries.
  * No suspicious metastatic lesions (no visceral lesions, no enlarged nodes outside the surgical basin).
* Age ≥18 years.
* ECOG performance status ≤ 1.
* No prior therapy for index pancreatic cancer.
* Patients must have adequate organ and marrow function as defined in protocol
* Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For 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, they are eligible if they have an undetectable HCV viral load.
* Patients with a prior malignancy (with all treatment completed at least 2 years prior to enrollment) whose natural history does not have the potential to interfere with the safety or efficacy assessment of this study are eligible.
* Women of child-bearing potential and fertile men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of active treatment.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients with uncontrolled intercurrent illness or comorbidities that would, in the opinion of the treating physician, prevent receipt of standard of care chemotherapy, radiation or surgery.
* Pregnant women or women who are breastfeeding are excluded from this study.
* Patients who are currently receiving any other investigational agents. Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
* Patients with psychiatric illness/social situations that would limit compliance with study requirements, per the PI's discretion.
* Patients who, in the opinion of the PI, will be unable to adhere to study requirements.