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Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer
This study is currently recruiting participants.
Verified by Wakayama Medical University, January 2008
Sponsors and Collaborators: Wakayama Medical University
Human Genome Center, Institute of Medical Science, University of Tokyo
Information provided by: Wakayama Medical University
ClinicalTrials.gov Identifier: NCT00622622
  Purpose

The purpose of this study is to evaluate the safety, tolerability and immune response of different doses of VEGFR2-169 emulsified with Montanide ISA 51 in combination with gemcitabine and to determine the recommended phase II dose.


Condition Intervention Phase
Pancreatic Cancer
 Biological: VEGFR2-169 and gemcitabine
 Phase I

MedlinePlus related topics: Cancer Pancreatic Cancer
Drug Information available for: Gemcitabine hydrochloride Gemcitabine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety Study
Official Title: Phase I Study of Gemcitabine With Antiangiogenic Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*2402 Derived From VEGFR2 in Patients With Unresectable, Locally Advanced, Recurrent or Metastatic Pancreatic Cancer

Further study details as provided by Wakayama Medical University:

Primary Outcome Measures:
  • Safety(toxicities as assessed by NCI CTCAE version 3) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • VEGFR2 peptide specific CTL induction in vitro [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • DTH to VEGFR2 peptide [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Changes in levels of regulatory T cells [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Objective response rate as assessed by RECIST criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 1 years ] [ Designated as safety issue: No ]
  • survival [ Time Frame: 1 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: November 2006
Estimated Study Completion Date: May 2008
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Phase I study: Experimental Biological: VEGFR2-169 and gemcitabine
Escalating doses of VEGFR2-169 will be administered by subcutaneous injection on days 1,8,15 and 22 of each 28-day treatment cycles(doses of 0.5,1.0,2.0mg/body are planned). Gemcitabine will be administered intravenously at a fixed dose of 1000mg/m2 on days 1,8 and 15. Repeated cycles of VEGFR2-169 and gemcitabine will be administered until patients develop progressive disease or unacceptable toxicity,or for maximum 2 cycles, whichever occurs first.

Detailed Description:

Vascular endothelial growth factor receptor 2(VEGFR2) is essential target for tumor angiogenesis, and VEGFR2-169 induces specific Cytotoxic T lymphocytes (CTL) against VEGFR2 expressed targets. VEGFR2-169 shows strong anti-tumor effects restricted to HLA-A*2402 in vitro, and this peptide induces CTL from cancer patients. 60% in Japanese population have HLA-A*2402. VEGFR2-169 is suitable for clinical trial, and gemcitabine has been approved against pancreatic cancer. Gemcitabine is reported to improve immune-response, therefore synergistic effect between vaccine therapy and chemotherapy will be expected. In this clinical trial, we evaluate the safety, tolerability and immune response of different doses of VEGFR2-169 emulsified with Montanide ISA 51 in combination with gemcitabine and to determine the recommended phase II dose of peptide.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

DISEASE CHARACTERISTICS

  1. locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer
  2. measurable disease by CT scan

PATIENT CHARACTERISTICS

  1. ECOG performance status 0-2
  2. Life expectancy > 3 months

  3. Laboratory values as follows

    • 2000/mm3 < WBC < 15000/mm3
    • Platelet count > 75000/mm3
    • Bilirubin < 3.0 mg/dl
    • Aspartate transaminase < 150 IU/L
    • Alanine transaminase < 150 IU/L
    • Creatinine < 3.0 mg/dl
  4. HLA-A*2402
  5. Able and willing to give valid written informed consent

Exclusion Criteria:

  1. Pregnancy(woman of childbearing potential:Refusal or inability to use effective means of contraception)
  2. Breastfeeding
  3. Active or uncontrolled infection
  4. Concurrent treatment with steroids or immunosuppressing agent
  5. Prior chemotherapy of gemcitabine
  6. Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks
  7. Serious or nonhealing wound, ulcer, or bone fracture
  8. Active or uncontrolled other malignancy
  9. Ileus
  10. Interstitial pneumonia
  11. Decision of unsuitableness by principal investigator or physician-in-charge
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00622622

Contacts
Contact: Hiroki Yamaue, MD +81-73-441-0613 yamaue-h@wakayama-med.ac.jp

Locations
Japan, Wakayama
Wakayama Medical University Hospital Recruiting
811-1 Kimiidera, Wakayama, Wakayama, Japan
Contact: Hiroki Yamaue, MD     +81-73-441-0613     yamaue-h@wakayama-med.ac.jp    
Principal Investigator: Hiroki Yamaue, MD            
Sponsors and Collaborators
Wakayama Medical University
Human Genome Center, Institute of Medical Science, University of Tokyo
Investigators
Study Chair: Hiroki Yamaue, MD Wakayama Medical University, Second Department of Surgery
  More Information

Publications:
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.
Li Y, Wang MN, Li H, King KD, Bassi R, Sun H, Santiago A, Hooper AT, Bohlen P, Hicklin DJ. Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. J Exp Med. 2002 Jun 17;195(12):1575-84. Erratum in: J Exp Med 2002 Aug 19;196(4):557.
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. Epub 2002 Nov 4.
Date Y, Kimura A, Kato H, Sasazuki T. DNA typing of the HLA-A gene: population study and identification of four new alleles in Japanese. Tissue Antigens. 1996 Feb;47(2):93-101.
Correale P, Cusi MG, Del Vecchio MT, Aquino A, Prete SP, Tsang KY, Micheli L, Nencini C, La Placa M, Montagnani F, Terrosi C, Caraglia M, Formica V, Giorgi G, Bonmassar E, Francini G. Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro. J Immunol. 2005 Jul 15;175(2):820-8. Erratum in: J Immunol. 2005 Nov 1;175(9):6235. Prete, Salvatore [corrected to Prete, Salvatore Pasquale].
Dauer M, Herten J, Bauer C, Renner F, Schad K, Schnurr M, Endres S, Eigler A. Chemosensitization of pancreatic carcinoma cells to enhance T cell-mediated cytotoxicity induced by tumor lysate-pulsed dendritic cells. J Immunother (1997). 2005 Jul-Aug;28(4):332-42.

Responsible Party: Wakayama Medical University ( Second Department of Surgery )
Study ID Numbers: WPR2-0710
Study First Received: February 13, 2008
Last Updated: February 13, 2008
ClinicalTrials.gov Identifier: NCT00622622  
Health Authority: Japan: Ministry of Health, Labor and Welfare

Study placed in the following topic categories:
Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases
Pancreatic Diseases
 Gastrointestinal Neoplasms
Endocrinopathy
Gemcitabine
Recurrence
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
 Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009



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