Vaccine Therapy, Cyclophosphamide, and Cetuximab in Treating Patients With Metastatic or Locally Advanced Pancreatic Cancer
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.
|Pancreatic Cancer||Drug: Cetuximab Biological: Pancreatic tumor vaccine Drug: Cyclophosphamide||Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Safety and Efficacy Trial of Lethally Irradiated Allogeneic Pancreatic Tumor Cells Transfected With the GM-CSF Gene in Combination With Erbitux (Cetuximab) for the Treatment of Advanced Pancreatic Adenocarcinoma|
- Safety of Combining the Pancreatic Tumor Vaccine in Sequence With Cyclophosphamide and Erbitux. Safety is Defined as the Number of Treatment-related Grade 3 or 4 Adverse Events Observed in Greater Than 5% of the Patient Population [ Time Frame: Continuous ]
|Study Start Date:||December 2005|
|Primary Completion Date:||February 2009 (Final data collection date for primary outcome measure)|
|Experimental: Cyclophosphamide, Pancreatic Tumor Vaccine, Cetuximab||
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.
Other Name: ErbituxBiological: Pancreatic tumor vaccine
Vaccine will be administered one day after cyclophosphamide (day 1) every three weeks for 6 cycles.
Other Names:Drug: Cyclophosphamide
Cyclophosphamide 250 mg/m2 will be administered one day prior to vaccination (day 0) every three weeks for 6 cycles.
Other Name: Cytoxan
- Determine the safety of pancreatic tumor vaccine, cyclophosphamide, and cetuximab in patients with metastatic or locally advanced adenocarcinoma of the pancreas.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00305760
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Principal Investigator:||Daniel A. Laheru, MD||Sidney Kimmel Comprehensive Cancer Center|