MR Guided Dose Escalated RT + Concurrent Chemotherapy in Unresectable Pancreatic Cancer

In this study the investigators want to find out more about the efficacy of giving higher
doses of radiation with concurrent chemotherapy in controlling unresectable pancreas cancers
than are used in either the pre-operative or post-operative setting. The investigators will
assess acute and late side effects (problems and symptoms) of radiation therapy given at
these higher doses of radiation (dose escalated) following full dose chemotherapy given
before the radiation and with concurrent chemotherapy for pancreas cancer. Radiation therapy
is given in higher doses that are limited by the proximity of normal organs to the radiation
dose distribution to improve the likelihood of controlling the tumor in the pancreas while
minimizing the risk of radiation injury to these organs. There are two chemotherapy drugs,
Capecitabine is an oral drug taken twice per day on the same day that radiation therapy is
given and Gemcitabine is an intravenous drug given once per week, during radiation therapy.
Everyone in this study will have already received chemotherapy alone first. Everyone in this
study will receive radiation therapy and concurrent chemotherapy.

Inclusion Criteria:

3.1 Conditions for Patient Eligibility

- 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.

- Patients 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.

- Heme Onc and CA 19-9/CEA within 14 days prior to study entry, as follows.

- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;

- Platelets ≥ 100,000 cells/mm3;

- 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;

- ALT or AST < 3 x upper limit of normal;

- Total bilirubin < 3.0 mg/dL;

- Alkaline phosphatase < 3 x upper limit of normal;

- Fasting blood glucose < 160 mg/dl.

- Negative serum pregnancy test (if applicable) within 14 days prior to study entry.

- Ability to swallow oral medications.

- Patients must have had at least 4 months of prior systemic chemotherapy.

- Patient 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 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.