HLA-A*0201 Restricted Peptide Vaccine Therapy With Gemcitabine With Gemcitabine in Patient Pancreatic Cancer (Phase1)

Phase 1 Study of HLA-A*0201 Restricted Antiangiogenic Peptide Vaccine Therapy Using Epitope Peptide Derived From VEGFR1 and VEGFR2 With Gemcitabine in Treating Patients With Unresectable, Recurrent, or Metastatic Pancreatic Cancer

The purpuse of this study is to assess toxicities of angiogenic peptide vaccine therapy with gemcitabine in treating HLA-A*0201 restricted patient with non-resectable pancreatic cancer.

Study Overview

• Status: Unknown
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Biological: VEGFR1, VEGFR2; Drug: Gemcitabine

Detailed Description

The prognosis of pancreatic cancer is extremely poor even with extensive surgery, chemotherapy or radiation. It has been required development of new treatment modalities. Immunotherapy is one of the encouraging modalities for cancer patients. The investigators have to assess its toxicities and immune responsiveness.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer
• Measurable disease by CT scan
• ECOG performance status 0-2
• Life expectancy > 3 months
• laboratory values as follows: 2,000/mm3 < WBC < 15,000/mm3, Platelet count >75,000/mm3, Total Bilirubin <1.5 mg/dl, Asparate transaminase <150IU/L, Alanine transaminase < 150 IU/L, Creatinine < 3.0mg/dl
• HLA-A*0201
• Able and willing to give valid written infromed consent

Exclusion Criteria:

• Pregnancy (women of childbearing potential: Refusal or inability to use effective means of contraception)
• Breast-feeder
• Active or uncontrolled infection
• Prior chemotherapy, radiation therapy, or immunotherapy within 4 weeks
• Serious or uncured wound
• Active or uncontrolled other malignancy
• Steroids or immunosuppressing agent dependent status
• Interstitial pneumonia
• Ileus
• Decision of unsuitableness by principal investigator or physician-in-charge

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 study; Interventions: Biological: VEGFR1, VEGFR2 Drug: Gemcitabine	Biological: VEGFR1, VEGFR2; One mg of each peptide will be administered subctaneously on days 1, 8, 15 and 22; Other Names: VEGFR1 and VEGFR2 specific epitope vaccine; Drug: Gemcitabine; Gemcitabine will be administered intravenously at a fixed dose of 1000mg/m2 on day 1, 8, 15.; Other Names: Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicities as assessed by NCI-CACAE ver3	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Differences of peptide specific CTL response in vitro among sequence of gemcitabine and peptide vaccine administration	3 months
CD8 population	3 months
Change in level of regulatory T cells	3 months
Objective response rate	1 year
Feasibility	1 year
Survival	1 year

Collaborators and Investigators

• Sponsor: Fukushima Medical University
• Collaborators: Human Genome Center, Institute of Medical Science, University of Tokyo
• Investigators: Study Chair: Mitsukazu Gotoh, MD & PhD, Fukushima Medical University, Department of Regeneration Surgery

Publications and helpful links

General Publications

• Ishizaki H, Tsunoda T, Wada S, Yamauchi M, Shibuya M, Tahara H. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 2006 Oct 1;12(19):5841-9. doi: 10.1158/1078-0432.CCR-06-0750.
• Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M, Tahara H. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005 Jun 1;65(11):4939-46. doi: 10.1158/0008-5472.CAN-04-3759.
• Niethammer AG, Xiang R, Becker JC, Wodrich H, Pertl U, Karsten G, Eliceiri BP, Reisfeld RA. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med. 2002 Dec;8(12):1369-75. doi: 10.1038/nm1202-794. Epub 2002 Nov 4.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): March 1, 2010
• Study Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: December 23, 2010
• First Submitted That Met QC Criteria: December 23, 2010
• First Posted (Estimate): December 24, 2010

Study Record Updates

• Last Update Posted (Estimate): December 24, 2010
• Last Update Submitted That Met QC Criteria: December 23, 2010
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: pancreatic cancer; gemcitabine; VEGFR; peptide vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: 689