Vaccine Therapy, Cyclophosphamide, and Cetuximab in Treating Patients With Metastatic or Locally Advanced Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety of pancreatic tumor vaccine, cyclophosphamide, and cetuximab in
           patients with metastatic or locally advanced adenocarcinoma of the pancreas.

      Secondary

        -  Determine the overall, progression-free, and event-free survival of patients treated
           with this regimen.

        -  Correlate specific in vivo parameters of immune response (e.g., mesothelin, prostate
           stem cell antigen [PSCA], mutated k-ras-specific T-cell responses) with clinical
           response in patients treated with this regimen.

        -  Correlate downstream targets of epidermal growth factor receptor (EGFR) signaling (e.g.,
           intratumor expression of Akt, Stat 3 and 5, mesothelin, mutated k-ras, and PSCA) with
           inhibition by cetuximab in patients treated with this regimen.

        -  Correlate inhibition of EGFR signaling (e.g., Stat 3 and 5) with improved specific
           mesothelin, PSCA, and mutated k-ras-specific T-cell responses in patients treated with
           this regimen.

      OUTLINE: This is an open-label study.

      Patients receive cyclophosphamide IV on day 0, sargramostim plasmid DNA pancreatic tumor
      vaccine intradermally on day 1, and cetuximab IV over 1-2 hours on days 1, 8, and 15.
      Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or
      unacceptable toxicity.

      Patients undergo blood collection and tumor biopsies periodically during study for biomarker
      correlative studies.

      At the completion of study treatment, patients are followed at 3 weeks and then every 4 weeks
      for 16 weeks.

      PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
    

Intervention name(s): Cetuximab; Pancreatic tumor vaccine; Cyclophosphamide
Intervention type(s): Drug; Biological; Drug
Intervention description(s): 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.
Other intervention name(s): Erbitux; PANC 10.05 pcDNA-1/GM-Neo and PANC 6.03 pcDNA-1/GM-Neo vaccine; GVAX; Cytoxan
Intervention MeSH terms: Cyclophosphamide; Cetuximab; Vaccines
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III pancreatic cancer; recurrent pancreatic cancer; duct cell adenocarcinoma of the pancreas; adenocarcinoma of the pancreas; stage IV pancreatic cancer