Vaccine Therapy, Cyclophosphamide, and Cetuximab in Treating Patients With Metastatic or Locally Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Cetuximab; Pancreatic tumor vaccine; Cyclophosphamide
Intervention description: Cetuximab will be administered at an initial dose of 400 mg/m2, followed by weekly doses of 250 mg/m2 for a total of 6 cycles that last 3 weeks each.; Vaccine will be administered one day after cyclophosphamide (day 1) every three weeks for 6 cycles.; Cyclophosphamide 250 mg/m2 will be administered one day prior to vaccination (day 0) every three weeks for 6 cycles.
Intervention MeSH terms: Cyclophosphamide; Cetuximab; Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage III pancreatic cancer; recurrent pancreatic cancer; duct cell adenocarcinoma of the pancreas; adenocarcinoma of the pancreas; stage IV pancreatic cancer

Summary:

      RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune
      response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in
      different ways. Some block the ability of tumor cells to grow and spread. Others find tumor
      cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop
      the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving
      vaccine therapy together with cyclophosphamide and cetuximab may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well vaccine therapy works when given together
      with cyclophosphamide and cetuximab in treating patients with metastatic or locally advanced
      pancreatic cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed ductal adenocarcinoma of the pancreas

               -  Mixed adenocarcinoma tumors eligible provided the predominant invasive component
                  of the tumor is adenocarcinoma

          -  The following histologic diagnoses are not eligible:

               -  Adenosquamous

               -  Squamous cell

               -  Colloid

               -  Islet cell

               -  Serous or mucinous cystadenoma or cystadenocarcinoma

               -  Carcinoid

               -  Small or large cell carcinoma

               -  Intraductal oncocytic papillary neoplasms

               -  Osteoclast-like giant cell tumors

               -  Acinar cell carcinoma

               -  Pancreatoblastoma

               -  Solid pseudopapillary tumors

               -  Undifferentiated small cell carcinoma

               -  Nonepithelial tumors (sarcoma, gastrointestinal stromal tumor, lymphoma)

               -  Adenocarcinomas of the ampulla, distal bile duct, or duodenum

          -  Metastatic or locally advanced disease that is refractory to standard therapy OR for
             which patient refused standard therapy

          -  Measurable disease defined as ≥ 1 lesion unidimensionally measured as ≥ 20 mm by
             conventional techniques or ≥ 10 mm by spiral CT scan

               -  No nonmeasurable disease only including, but not limited to, the following:

                    -  Bone lesions

                    -  Leptomeningeal disease

                    -  Ascites

                    -  Pleural or pericardial effusion

                    -  Inflammatory breast disease

                    -  Lymphangitis cutis/pulmonis

                    -  Abdominal masses that are not confirmed and followed by imaging techniques

                    -  Cystic lesions

          -  No known active or untreated brain metastases

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-1

          -  WBC ≥ 3,500/mm^3

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Hemoglobin ≥ 9 g/dL

          -  Platelet count ≥ 90,000/mm^3

          -  Creatinine ≤ 2.0 mg/dL

          -  Bilirubin ≤ 2 mg/dL

          -  ALT and AST ≤ 5 times upper limit of normal (ULN)

          -  Alkaline phosphatase ≤ 5 times ULN

          -  No active infection

          -  No uncontrolled medical condition that would potentially increase the risk of
             toxicities or complications of study therapy

          -  No gastrointestinal tract disease resulting in an inability to take oral medication or
             a requirement for IV alimentation

          -  No active peptic ulcer disease

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 4 weeks after
             completion of study treatment

          -  No other malignancy within the past 5 years except for nonmelanomatous skin cancer,
             superficial bladder cancer, or carcinoma in situ of the cervix

          -  HIV negative

          -  No active autoimmune disease or prior autoimmune disease requiring medical treatment
             with systemic immunosuppressants including any of the following:

               -  Inflammatory bowel disease

               -  Systemic vasculitis

               -  Scleroderma

               -  Psoriasis

               -  Multiple sclerosis

               -  Hemolytic anemia or immune thrombocytopenia

               -  Rheumatoid arthritis

               -  Systemic lupus erythematosus

               -  Sjögren's syndrome

               -  Sarcoidosis

               -  Asthma or chronic obstructive pulmonary disease that does not require systemic
                  corticosteroids or routine use of inhaled steroids allowed

          -  No known or suspected hypersensitivity to sargramostim (GM-CSF), cyclophosphamide,
             pentastarch, corn, or DMSO

          -  No prior severe infusion reaction (> grade 3) to a monoclonal antibody

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  More than 1 month since prior adjuvant chemotherapy

          -  More than 4 weeks since prior surgery except for minor procedures (e.g., dental work,
             skin biopsy) and biliary stent placement

          -  No prior surgical procedures affecting absorption

          -  More than 4 weeks since prior radiotherapy

          -  More than 1 month since prior participation in an investigational new drug study

          -  No unresolved chronic toxicity (except alopecia) from prior anticancer therapy

          -  More than 28 days since prior systemic steroids

          -  No concurrent systemic steroids or immunosuppressive drugs

               -  Topical, inhaled, and intra-articular steroids allowed

          -  No other concurrent anticancer vaccine therapy

          -  No other concurrent chemotherapy, immunotherapy, radiotherapy, gene therapy, biologic
             therapy, or investigational therapy