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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


N/A
18 Years
N/A
Open (Enrolling)
Both
Pancreatic Cancer

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Trial Information

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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed adenocarcinoma of the head, neck, or uncinate process of the pancreas

- Stage I or II disease

- Surgically resectable disease (R0 or R1) by spiral CT scan

- No distant metastases

- A clear fat plane is present around the celiac and superior mesenteric arteries

- Patent superior mesenteric and portal veins

- Candidate for a pancreaticoduodenectomy

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Hemoglobin ≥ 9 g/dL

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Serum creatinine ≤ 2 mg/dL

- AST and ALT ≤ 2 times upper limit of normal (ULN)

- Amylase ≤ 2 times ULN

- Alkaline phosphatase ≤ 5 times ULN

- Hyperbilirubinemia secondary to tumor-associated extrahepatic biliary obstruction
allowed

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for ≥ 4 weeks after the
completion of study treatment

- No history of autoimmune disease, including systemic lupus erythematosus,
sarcoidosis, rheumatoid arthritis, glomerulonephritis, or vasculitis

- No uncontrolled medical problems

- No active infections

- No other cancer within the past 5 years except for superficial bladder cancer,
nonmelanoma skin cancer, or low-grade prostate cancer not requiring therapy

PRIOR CONCURRENT THERAPY:

- More than 28 days since prior anticancer therapy

- No prior cancer immunotherapy, including the same pancreatic cancer vaccine used in
this study

- More than 28 days since prior systemic steroid therapy or immunosuppressive therapy

- No systemic steroid therapy or immunosuppressive therapy during and within 28 days
after vaccine administration

- No other concurrent immunotherapy, chemotherapy, radiotherapy, gene therapy, biologic
therapy, or investigational therapy for the treatment of pancreatic cancer

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety, as measured by local and systemic toxicity according to NCI CTCAE v3.0

Outcome Description:

During the period of the study.

Outcome Time Frame:

About 2 years

Safety Issue:

Yes

Principal Investigator

Daniel A. Laheru, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

JHOC-J0810, CDR0000600355

NCT ID:

NCT00727441

Start Date:

July 2008

Completion Date:

March 2014

Related Keywords:

  • Pancreatic Cancer
  • adenocarcinoma of the pancreas
  • stage I pancreatic cancer
  • stage II pancreatic cancer
  • Adenocarcinoma
  • Pancreatic Neoplasms

Name

Location

Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410