Stereotactic Radiation, Nelfinavir Mesylate & Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Cancer

Inclusion Criteria:

* The time between other investigational agents and enrollment on this study is at least 30 days
* Pathologically confirmed adenocarcinoma of the pancreas
* Patients have localized or locally advanced disease with no evidence of distant metastases
* The maximum dimension of the tumor must be =\< 8 cm
* Karnofsky Performance Status of 60% or better
* Patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation
* Patients who received chemotherapy \> 5 years ago for malignancies other than pancreatic cancer are eligible, provided that chemotherapy was completed \> 5 years ago and that there is no evidence of the second malignancy at the time of study entry
* Patients who received radiation therapy \> 5 years ago for malignancies other than pancreatic cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed \> 5 years ago and that there is no evidence of the second malignancy at the time of study entry
* All malignant disease must be able to be encompassed within a single irradiation field
* All patients must have radiographically assessable disease
* Patients must have a absolute granulocyte count (AGC) greater than or equal to 1500/uL and platelet count greater than or equal to 100,000/uL
* Patients must have a serum creatinine less than or equal to 2 mg/dL and total bilirubin less than or equal to 2.0 mg/dL in the absence of biliary obstruction
* If the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of biliary stent (7 French or greater) or percutaneous transhepatic drainage are acceptable; once biliary drainage has been established, institution of gemcitabine therapy may proceed when the total bilirubin falls to below 4.0 mg/dL
* The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
* Patients may have had prior chemotherapy for pancreatic cancer
* Any prior therapy is acceptable except radiation to the abdomen

Exclusion Criteria:

* Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study: carbamazepine; phenobarbital; phenytoin; rifabutin; sildenafil; atorvastatin; cyclosporine; tacrolimus; sirolimus; methadone; ethinyl estradiol; azithromycin
* Patients who can not undergo staging laparoscopy and marker implantation; this may include patients with a prior history of multiple abdominal operations in which laparoscopy may not be technically feasible or potentially harmful
* The patient is eligible if they have a common bile duct stent adjacent to the tumor that may be used as an internal marker, or if the patient has already had a staging laparoscopy without marker implantation and the markers can be implanted (by interventional radiology) prior to the beginning of radiation therapy
* History of allergy to chemotherapy agents or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
* Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety
* Patients with human immunodeficiency virus (HIV) infection, or hepatic insufficiency
* Patients may not be receiving or have received any other investigational agents during/or within 1 month prior to treatment with NFV (nelfinavir mesylate)
* Patients who can not take oral medications
* Patients with active duodenal ulcer or bleeding or history of a gastrointestinal fistula or perforation or other significant bowel problems (severe nausea, vomiting, inflammatory bowel disease and significant bowel resection)
* Patients with prior malignancy will be excluded EXCEPT for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years
* Patients receiving the following drugs that are contraindicated with NFV will be excluded: amiodarone; quinidine; rifampin; dihydroergotamine; ergonovine; ergotamine; methylergonovine; St. John's wort (hypericum perforatum); lovastatin; simvastatin; pimozide; midazolam; triazolam
* Pregnant and nursing women are excluded from this study