Human Leukocyte Antigen-A*0201-Restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer - Full Text View

Sponsor:	Tokyo University
Collaborator:	Human Genome Center, Institute of Medical Science, University of Tokyo
Information provided by:	Tokyo University
ClinicalTrials.gov Identifier:	NCT00683085

Purpose

Feasibility and efficacy of combined modality intervention using conventional dose of gemcitabine with anti-angiogenic peptide vaccination targeting tumor-vessel specific VEGFR1 should be determined in case of advanced/inoperable or therapy-resistant pancreatic cancer patients.

Gemcitabine 1,000mg/m2 (body surface area) will be administered on day 1, day 8, day 15, day 29, day 36, and day 43, respectively.

VEGFR1-derived HLA-A*0201-restricted peptide (VEGFR1-A02-770; TLFWLLLTL) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8 weeks (total 16 doses).

Condition	Intervention	Phase
Pancreatic Cancer Pancreas Neoplasms	Biological: VEGFR1-A02-770 (TLFWLLLTL)	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase Ⅰ/Ⅱ Trial of Human Leukocyte Antigen (HLA)-A*0201-Restricted Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Derived Peptide Vaccination Combined With Conventional Dose of Gemcitabine for Advanced 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 Tokyo University:

Primary Outcome Measures:

Phase 1; safety (NCI CTCAE v.3) Phase 2; time to progression (RECIST) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immune response (ELISPOT, FACS for perforin/FOXP3, in vitro CTL assay, etc.) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Tumor regression (RECIST by imaging study, tumor marker, etc.) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment:	14
Study Start Date:	May 2008
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental VEGFR1-derived HLA-A*0201-restricted peptide (VEGFR1-A2-770) 1mg emulsified with Montanide ISA51 will be subcutaneously injected 2ce weekly for 8 weeks (total 16 doses) combined with conventional dose (1,000mg/m2 BSA) of gemcitabine on 1st, 2nd, 3rd, 5th, 6th, and 7th weeks.	Biological: VEGFR1-A02-770 (TLFWLLLTL) VEGFR1-derived HLA-A*0201-restricted peptide (VEGFR1-A2-770) 1mg emulsified with Montanide ISA51 will be subcutaneously injected 2ce weekly for 8 weeks (total 16 doses) combined with conventional dose (1,000mg/m2 BSA) of gemcitabine on 1st, 2nd, 3rd, 5th, 6th, and 7th weeks.

Detailed Description:

HLA-A*0201-restricted VEGFR1-specific cytotoxic T lymphocyte (CTL) responses were obtained from HLA-A2/Kd transgenic murine model.

HLA-A*0201-restricted VEGFR1-specific CTL clones were also obtained from peripheral blood mononuclear cells of healthy volunteer donors.

These CTL clones showed potent anti-tumor CTL responses in HLA class Ⅰ-restricted manner in vitro.

Vaccination of HLA-A*0201-restricted VEGFR1-specific peptide to A2/Kd transgenic mice markedly suppress the tumor-induced angiogenesis and tumor growth in vivo.

Eligibility

Ages Eligible for Study:	20 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Heterozygote or homozygote of HLA-A*0201 allele
Inoperable or recurrent pancreatic cancer with or without any prior therapy
Difficult to continue the prior therapy due to treatment-related toxicities
ECOG performance status 0-2
Evaluable primary or metastatic lesion with RECIST criteria
Clearance period from prior therapy more than 4 weeks
Life expectancy more than 3 months
Laboratory values as follows 2,000/μL<WBC<15,000/μL Platelet count>100,000/μL AST<150IU/L ALT<150IU/L Total bilirubin<3.0mg/dl Serum creatinine<3.0mg/dl

Exclusion Criteria:

Pregnancy (refusal or inability to use effective contraceptives)
Breastfeeding
Active or uncontrolled infection
Systemic use of corticosteroids or immunosuppressants
Uncontrollable brain metastasis and/or meningeal infiltration
Unhealed external wound
Possibilities of complicated paralytic ileus or interstitial pneumonitis
Decision of not eligible determined by principal investigator or attending doctor

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00683085

Locations

Japan, Tokyo
Research Hospital, The Institute of Medical Science, The University of Tokyo
Minato-ku, Tokyo, Japan, 108-8639

Sponsors and Collaborators

Tokyo University

Human Genome Center, Institute of Medical Science, University of Tokyo

Investigators

Study Director:

Naohide Yamashita, MD, PhD

Director, Research Hospital, Institute of Medical Science, Tokyo University

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Nagayama H, Sato K, Morishita M, Uchimaru K, Oyaizu N, Inazawa T, Yamasaki T, Enomoto M, Nakaoka T, Nakamura T, Maekawa T, Yamamoto A, Shimada S, Saida T, Kawakami Y, Asano S, Tani K, Takahashi TA, Yamashita N. Results of a phase I clinical study using autologous tumour lysate-pulsed monocyte-derived mature dendritic cell vaccinations for stage IV malignant melanoma patients combined with low dose interleukin-2. Melanoma Res. 2003 Oct;13(5):521-30.

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.

Responsible Party:	Research Hospital, The Institute of Medical Science, The University of Tokyo ( Naohide Yamashita MD,PhD )
Study ID Numbers:	IMSUT-PPKVEGFR10201
Study First Received:	May 16, 2008
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00683085 History of Changes
Health Authority:	Japan: Ministry of Education, Culture, Sports, Science and Technology

Keywords provided by Tokyo University:

cancer
pancreas
advanced
peptide
vaccination
VEGFR1

HLA
gemcitabine
IFA
Cancer of Pancreas
Neoplasms, Pancreas
Pancreas Cancer

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Digestive System Neoplasms
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Endocrine System Diseases
Enzyme Inhibitors

Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Digestive System Diseases
Radiation-Sensitizing Agents
Therapeutic Uses
Pancreatic Diseases
Gemcitabine
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010