Chemotherapy, Stereotactic Body Radiation Therapy & Nelfinavir Mesylate in Locally Advanced Pancreatic Cancer
Condition: Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: 4-Dimensional Computed Tomography; Fluorouracil; Gemcitabine Hydrochloride; Laboratory Biomarker Analysis; Leucovorin Calcium; Nelfinavir Mesylate; Oregovomab; Stereotactic Body Radiation Therapy; Therapeutic Conventional Surgery
Intervention description: Correlative studies; Given IV; Given IV; Correlative studies; Given IV; Given PO; Given IV; Undergo SBRT; Undergo surgical resection
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Nelfinavir; Gemcitabine; Fluorouracil; Oregovomab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well combination chemotherapy with or without oregovomab
      followed by stereotactic body radiation therapy (SBRT) and nelfinavir mesylate works in
      treating patients with pancreatic cancer that has spread to nearby organs or tissues. Drugs
      used in chemotherapy, such as gemcitabine hydrochloride, leucovorin calcium, and
      fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal
      antibodies, such as oregovomab, can block tumor growth in different ways by targeting certain
      cells. Stereotactic body radiation therapy is a specialized radiation therapy that sends
      x-rays directly to the tumor using smaller doses over several days and may cause less damage
      to normal tissue. Drugs, such as nelfinavir mesylate, may make tumor cells more sensitive to
      radiation therapy. Giving combination chemotherapy with or without oregovomab followed by
      SBRT and nelfinavir mesylate may kill more tumor cells.
    

Eligibility criteria:

        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