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.