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

Inclusion Criteria:

* Pathologically confirmed adenocarcinoma of the pancreas; patients have resectable borderline resectable disease, or unresectable disease with no evidence of distant metastases or peritoneal disease; the maximum dimension of the tumor must be =\< 10 cm
* Karnofsky performance status of 60% or better
* 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
* Absolute neutrophil count (ANC) greater than or equal to 1500/uL
* Platelet count greater than or equal to 100,000/uL
* Serum creatinine less than or equal to 2.0 mg/dL
* 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 =\< 4.0 mg/dL; patients with biliary or gastroduodenal obstruction must have drainage or surgical bypass prior to starting chemoradiation
* 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
* No prior therapy with the exception of 1 cycle of chemotherapy based on current diagnosis and clinical condition
* Patients must have CA125 level \>= 10 to participate in the immunotherapy aspect of the trial and receive oregovomab; if the patient has CA125 \>= 10 who is not eligible to receive oregovomab (e.g. allergic to the drug) but is eligible for the rest of treatment, this patient should be accrued to the part of protocol without oregovomab

Exclusion Criteria:

* Patients who cannot undergo staging laparoscopy; for example, 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
* Patients with a known allergy to murine proteins or have had a documented anaphylactic reaction or allergy to any of chemotherapy agents used in this protocol, oregovomab, or to antiemetics appropriate for administration in conjunction with protocol-directed therapy
* 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 therapy program outlined in this protocol with reasonable safety
* Pregnant and nursing women are excluded from this study
* 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 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 known human immunodeficiency virus (HIV) infection, or hepatic insufficiency
* Patients who cannot take oral medications
* Patients may not be receiving or have received any other investigational agents during/or within 1 month prior to treatment with oregovomab or nelfinavir
* Patients with an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus \[SLE\], ulcerative colitis, Crohn's disease, multiple sclerosis \[MS\], ankylosing spondylitis)
* Patients with a recognized acquired, hereditary, or congenital immunodeficiency disease including cellular immunodeficiency's, hypogammaglobulinemia or dysgammaglobulinemia
* Patients receiving the following drugs that are contraindicated with nelfinavir (NFV) (VIRACEPT) will be excluded if they cannot be change or discontinued; drugs that should not be coadministered with Viracept:

  * Antiarrhythmics: amiodarone, quinidine
  * Antimycobacterial: rifampin
  * Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine
  * Herbal products: St. John's wort (hypericum perforatum)
  * 3-hydroxy-3-methyl-glutaryl (HMG)-acetyl coenzyme A (CoA) reductase inhibitors: lovastatin, simvastatin
  * Neuroleptic: pimozide
  * Sedative/hypnotics: midazolam, triazolam
* Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study:

  * Anti-convulsants: carbamazepine, phenobarbital
  * Anti-convulsant: phenytoin; phenytoin plasma/serum concentrations should be monitored; phenytoin dose may require adjustment to compensate for altered phenytoin concentration
  * Anti-mycobacterial: rifabutin; it is recommended that the dose of rifabutin be reduced to one-half the usual dose when administered with VIRACEPT; 1250 mg BID is the preferred dose of VIRACEPT when coadministered with rifabutin
  * Erectile dysfunction agent: sildenafil; sildenafil shall not exceed a maximum single dose of 25 mg in a 48 hour period
  * HMG-CoA reductase inhibitor: atorvastatin; use lowest possible dose of atorvastatin with careful monitoring, or consider other HMG-CoA reductase inhibitors such as pravastatin or fluvastatin in combination with VIRACEPT
  * Immunosuppressants: cyclosporine, tacrolimus, sirolimus
  * Narcotic analgesic: methadone; dosage of methadone may need to be increased when coadministered with VIRACEPT
  * Oral contraceptive: ethinyl estradiol; alternative or additional contraceptive measures should be used when oral contraceptives and VIRACEPT are coadministered
  * Macrolide antibiotic: azithromycin; dose adjustment of azithromycin is not recommended, but close monitoring for known side effects such as liver enzyme abnormalities and hearing impairment is warranted