Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer - Full Text View

Sponsor:	Wakayama Medical University
Collaborator:	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

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

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 ]

Enrollment:	21
Study Start Date:	November 2006
Study Completion Date:	February 2009
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.

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

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

PATIENT CHARACTERISTICS

ECOG performance status 0-2
Life expectancy > 3 months
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
HLA-A*2402
Able and willing to give valid written informed consent

Exclusion Criteria:

Pregnancy(woman of childbearing potential:Refusal or inability to use effective means of contraception)
Breastfeeding
Active or uncontrolled infection
Concurrent treatment with steroids or immunosuppressing agent
Prior chemotherapy of gemcitabine
Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks
Serious or nonhealing wound, ulcer, or bone fracture
Active or uncontrolled other malignancy
Ileus
Interstitial pneumonia
Decision of unsuitableness by principal investigator or physician-in-charge

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00622622

Locations

Japan, Wakayama
Wakayama Medical University Hospital
811-1 Kimiidera, Wakayama, Wakayama, Japan

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 17, 2009
ClinicalTrials.gov Identifier:	NCT00622622 History of Changes
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Gemcitabine

Endocrine Gland Neoplasms
Digestive System Neoplasms
Growth Substances
Endocrine System Diseases
Enzyme Inhibitors
Angiogenesis Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Pancreatic Diseases

ClinicalTrials.gov processed this record on November 25, 2009