A Randomized Three-arm Neoadjuvant and Adjuvant Feasibility and Toxicity Study of a GM-CSF Secreting Allogeneic Pancreatic Cancer Vaccine Administered Either Alone or in Combination With Either a Single Intravenous Dose or Daily Metronomic Oral Doses of Cyclophosphamide for the Treatment of Patients With Surgically Resected Adenocarcinoma of the Pancreas
OBJECTIVES:
Primary
- To evaluate the safety and feasibility of a GVAX pancreatic cancer vaccine (GM-CSF
gene-transfected allogeneic pancreatic cancer vaccine) when administered alone or in
combination with a single intravenous dose or daily metronomic oral doses of
cyclophosphamide as neoadjuvant and adjuvant treatment in patients with resectable
stage I or II adenocarcinoma of the head, neck, or uncinate process of the pancreas.
- To assess the immune cell infiltrates, particularly T-regulatory cells (Tregs) and CD4+
and CD8+ effector T cells, after neoadjuvant GVAX pancreatic cancer vaccination.
- To assess the changes in the number and function of peripheral mesothelin-specific CD8+
T cells and CD4+, FoxP3+, and GITR+ Tregs after each GVAX pancreatic cancer vaccination
when administered alone or in combination with a single dose or metronomic doses of
cyclophosphamide.
Secondary
- To estimate disease-free and overall survival of patients treated with these regimens.
- To estimate the effect of immune parameters on disease-free and overall survival of
these patients.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
- Arm A: Patients receive GVAX pancreatic cancer vaccine intradermally (ID) on day 1 and
undergo pancreaticoduodenectomy on day 15. Approximately 6-10 weeks after surgery,
patients receive an additional dose of the vaccine. Beginning approximately 1 month
after vaccination, patients receive standard adjuvant chemoradiotherapy comprising
gemcitabine, fluorouracil or capecitabine, and radiotherapy over 26-28 weeks. Beginning
approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive the
vaccine on day 1. Treatment with the vaccine repeats every 28 days for 4 courses.
- Arm B: Patients receive low-dose cyclophosphamide IV on day 0 and GVAX pancreatic
cancer vaccine ID on day 1. Patients undergo pancreaticoduodenectomy on day 15.
Approximately 6-10 weeks after surgery, patients receive low-dose cyclophosphamide IV
on day 0 and the vaccine on day 1. Beginning approximately 1 month after vaccination,
patients receive standard adjuvant chemoradiotherapy comprising gemcitabine,
fluorouracil or capecitabine, and radiotherapy over 26-28 weeks. Beginning
approximately 4-8 weeks after the completion of chemoradiotherapy, patients receive
low-dose cyclophosphamide IV on day 0 and the vaccine on day 1. Treatment with
cyclophosphamide and the vaccine repeats every 28 days for 4 courses.
- Arm C: Patients receive GVAX pancreatic cancer vaccine ID on day 1 and low-dose oral
cyclophosphamide twice daily on days 1-7. Patients undergo pancreaticoduodenectomy on
day 15. Approximately 6-10 weeks after surgery, patients receive the vaccine on day 1
and low-dose oral cyclophosphamide twice daily on days 1-7 and 15-21. Beginning
approximately 1 month after vaccination, patients receive standard adjuvant
chemoradiotherapy comprising gemcitabine, fluorouracil or capecitabine, and
radiotherapy over 26-28 weeks. Beginning approximately 4-8 weeks after the completion
of chemoradiotherapy, patients receive the vaccine on day 1 and low-dose oral
cyclophosphamide twice daily on days 1-7 and 15-21. Treatment with the vaccine and
cyclophosphamide repeats every 28 days for 4 courses.
Patients undergo blood sample collection periodically for correlative laboratory studies,
including immune cell analysis. Immune cell analysis includes monitoring the quantitative
change of peripheral blood lymphocytes, including regulatory T cells (Tregs), and functional
analysis of T-cell immune response. Tumor tissue samples collected at the time of surgery
are analyzed for tumor antigens and infiltrating immune cells by immunohistochemistry and
quantitative real-time PCR.
After completion of study treatment, patients are followed periodically.
Interventional
Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety, as measured by local and systemic toxicity according to NCI CTCAE v3.0
During the period of the study.
About 2 years
Yes
Daniel A. Laheru, MD
Principal Investigator
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
JHOC-J0810, CDR0000600355
NCT00727441
July 2008
March 2014
Name | Location |
---|---|
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |