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Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Undergoing Chemotherapy and Radiation Therapy for Stage I or Stage II Pancreatic Cancer That Can Be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00727441
First received: August 1, 2008
Last updated: November 17, 2014
Last verified: March 2014

August 1, 2008
November 17, 2014
July 2008
March 2015   (final data collection date for primary outcome measure)
  • Safety, as measured by local and systemic toxicity according to NCI CTCAE v3.0 [ Time Frame: About 2 years ] [ Designated as safety issue: Yes ]
    During the period of the study.
  • Feasibility [ Time Frame: About 2 years ] [ Designated as safety issue: No ]
    During the period of the study.
  • Immune response [ Time Frame: Unknown ] [ Designated as safety issue: No ]
    May continue beyond the period of the study.
  • Safety, as measured by local and systemic toxicity according to NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Feasibility [ Designated as safety issue: No ]
  • Immune response [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00727441 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: Unknown ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Unknown ] [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Undergoing Chemotherapy and Radiation Therapy for Stage I or Stage II Pancreatic Cancer That Can Be Removed by Surgery
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

RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective immune response to kill pancreatic cancer 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. Giving vaccine therapy together with cyclophosphamide may kill more tumor cells. It is not yet known whether vaccine therapy is more effective with or without cyclophosphamide in treating patients with pancreatic cancer.

PURPOSE: This randomized clinical trial is studying the side effects of vaccine therapy and to see how well it works when given with or without cyclophosphamide in treating patients undergoing chemotherapy and radiation therapy for stage I or stage II pancreatic cancer that can be removed by surgery.

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
Not Provided
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Cancer
  • Biological: GVAX pancreatic cancer vaccine
    Given intradermally
  • Drug: cyclophosphamide
    Given IV
  • Experimental: 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.
    Intervention: Biological: GVAX pancreatic cancer vaccine
  • Experimental: 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.
    Interventions:
    • Biological: GVAX pancreatic cancer vaccine
    • Drug: cyclophosphamide
  • Experimental: 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.
    Intervention: Biological: GVAX pancreatic cancer vaccine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
87
March 2016
March 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States
 
NCT00727441
JHOC-J0810, CDR0000600355, P30CA006973, JHOC-J0810, JHOC_NA_00015858
Yes
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Daniel A. Laheru, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP