Exploratory Trial of Immunochemoradiotherapy for Locally Advanced Pancreatic Adenocarcinoma

Inclusion Criteria:

Pancreatic adenocarcinoma proven by biopsy or cytology Locally advanced, unresectable
disease with absence of distant metastatic disease. The presence of non-regional
retroperitoneal or abdominal adenopathy is acceptable for inclusion.

OR

Borderline resectable pancreatic adenocarcinoma (any of the following):

- Tumor abutment or encasement of a short segment of hepatic artery (without evidence
of tumor extension to the celiac artery) that is amenable to resection and
reconstruction

- Tumor abutment of the superior mesenteric artery involving 180 degrees or less of the
circumference of the artery and without encasement

- Impingement or narrowing of the superior mesenteric vein/portal vein or short-segment
(< 2 cm) occlusion of the superior mesenteric vein, portal vein, or their confluence
with a suitable option for vascular reconstruction

- Eastern Cooperative Oncology Group(ECOG)Performance Status 0 or 1

- Ability to give informed consent and comply with the protocol

- Women of childbearing potential must have a negative pregnancy test and must avoid
becoming pregnant while on treatment. Men must avoid fathering a child while on
treatment.

- Patients with a history of psychiatric illness must be judged able to understand
fully the investigational nature of the study and the risks associated with the
therapy.

Exclusion Criteria:

- Age < 18 years

- History of other malignancy in the past 2 years except carcinoma in situ of the
cervix or bladder, or non-melanomatous skin cancer

- Previous chemotherapy or radiation therapy for pancreatic cancer or previous
radiation therapy to the target field

- Clinically active autoimmune disease or active infection

- History of heart attack (within 90 days) or stroke (within 6 months), or presence of
hypertension requiring change in blood pressure medications in the last 4 weeks,
hypotension, uncontrolled arrhythmias, heart failure (New York Heart Association
(NYHA) Functional Classification ≥ Class 2 in last 6 months), unstable angina or
angina occurring during sexual activity.

- Use of "nitrates" or nitroglycerin.

- History of hereditary degenerative retinal disorders including retinitis pigmentosa.

- Chronic systemic corticosteroid use at supra-physiologic doses (prednisone > 10 mg a
day or equivalent)

- Use of recreational drugs called "poppers" like amyl nitrite and butyl nitrite.

- Laboratory values (performed within 14 days prior to enrollment) as follows:

- Neutrophil count < 1500 cells/µL

- Hemoglobin < 9 gm/dL (patients may be transfused to establish eligibility)

- Platelet count < 100,000 cells/µL

- Significant coagulopathy (INR > 1.5)

- Significant liver or renal dysfunction

- Other medical or psychiatric conditions that in the opinion of the Principal
Investigator would preclude safe participation in protocol.