MR Guided Phase II Radiotherapy Dose Escalation in Unresectable Non-Metastatic Pancreatic Cancer

Inclusion Criteria:

* Pathologically confirmed (histologic or cytologic), locally advanced, adenocarcinoma of the pancreas; patients must have unresectable disease based on institutional standardized criteria of unresectability or medical inoperability.
* Participants with and without regional adenopathy are eligible.
* No distant metastases, based upon the following minimum diagnostic workup:
* History/physical examination, including collection of weight and vital signs, within 28 days prior to study entry;
* Abdominal/pelvic CT scan with IV contrast within 21 days prior to study entry;
* Chest CT scan, or X-ray within 21 days prior to study entry.
* Abdominal/pelvic MR prior to radiation with perfusion and diffusion- weighted sequences and MR and CT sim for radiation planning Pet scan within 21 days prior to study entry, Functional renal study.
* Zubrod performance status 0-1 within 1 week of study entry.
* Age ≥ 18.
* Hematology and cancer antigen (CA) 19-9 / carcinoembryonic antigen (CEA) within 14 days prior to study entry, as follows.
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3;
* Platelets ≥ 100,000 cells/mm\^3;
* Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.);
* Serum creatinine ≤ 1.5 mg/dl;
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 3 x upper limit of normal (ULN);
* Total bilirubin \< 3.0 mg/dL;
* Alkaline phosphatase \< 3 x ULN;
* Fasting blood glucose \< 160 mg/dl.
* Negative serum pregnancy test (if applicable) within 14 days prior to study entry.
* Ability to swallow oral medications.
* Participants must have had at least 4 months of prior systemic chemotherapy.
* Participants must provide study specific informed consent prior to study entry.
* Women of childbearing potential and male participants who are sexually active must practice adequate contraception.

Exclusion criteria:

* Distant metastatic disease, second malignancy or peritoneal seeding;
* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
* Any major surgery within 28 days prior to study entry
* Severe, active co-morbidity, defined as follows:
* Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
* Transmural myocardial infarction within 3 months prior to study entry;
* Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
* Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration;
* Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function;
* Any unresolved bowel or bile duct obstruction;
* Major resection of the stomach or small bowel that could affect the absorption of capecitabine
* Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease Control (CDC) definition;
* Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception during the course of the study and for women, for 3 months after the last study drug administration.
* Women who are lactating at the time of registration and who plan to be lactating through 3 months after the last study drug administration.
* Prior allergic reaction to capecitabine or gemcitabine
* Inability to undergo an MR of the abdomen/pelvis
* Participation in another clinical treatment trial while on study.