People with pancreatic cancer that cannot be cured by surgery are being asked to participate in this study.

The purpose of this study is to test the ability of the radiation oncologists to administer Cyberknife therapy along with Gemcitabine chemotherapy for patients with pancreatic cancer. Radiation and Gemcitabine are both effective at killing cancer cells but they generally cannot be given at the same time. Cyberknife therapy is highly focused radiation that is being used extensively at Georgetown University and around the United States to treat a number of cancers. It is believed that because Cyberknife is so highly focused it can be given safely with regular doses of chemotherapy to attack cancer cells in two ways at the same time.

This research is being done because it is not known if using Cyberknife with chemotherapy will be a safe way to treat pancreatic cancer.

This is a single arm, open-label pilot study of Cyberknife plus Gemcitabine in 10 patients with locally advanced pancreatic cancer who have not received prior local or systemic therapy for their pancreatic cancer.

Inclusion Criteria:

• Histologically proven unresectable, non-metastatic pancreatic adenocarcinoma with measurable or evaluable disease and without involvement of the duodenum
• Performance Status 0-2
• No prior anticancer therapy for pancreatic adenocarcinoma
• No prior anticancer therapy of any kind within the last 5 years
• Adequate hepatic, bone marrow, and renal function
• Life expectance of > 12 weeks
• Women of childbearing potential must have a negative serum pregnancy test

Exclusion Criteria:

• Duodenal involvement of pancreatic cancer
• Metastatic cancer
• Active severe infection, or known chronic infection with HIV, hepatitis B virus, or hepatitis C virus
• Cardiovascular disease including unstable angina, therapy for life-threatening ventricular arrhythmia, myocardial infarction, stroke, or congestive heart failure within the last 6 months
• Life-threatening visceral disease or other severe concurrent disease
• Pregnant or breastfeeding
• Anticipated patient survival under 3 months
• Another active malignancy within the past 5 years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin.