Clinical trial NCT00305760
Conditions: Pancreatic Cancer
Keywords: stage III pancreatic cancer recurrent pancreatic cancer duct cell adenocarcinoma of the pancreas adenocarcinoma of the pancreas stage IV pancreatic cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2005-12-01; Completion date: 2009-03-01
Enrollment: 60 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: None
Interventions: intervention 1: Cetuximab intervention 2: Pancreatic tumor vaccine intervention 3: Cyclophosphamide
Intervention descriptions: intervention 1: 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. intervention 2: Vaccine will be administered one day after cyclophosphamide (day 1) every three weeks for 6 cycles. intervention 3: Cyclophosphamide 250 mg/m2 will be administered one day prior to vaccination (day 0) every three weeks for 6 cycles.

Protocol documents: