Human Leukocyte Antigen-A*2402-Restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer - Full Text View

Purpose

Feasibility and efficacy of combined modality intervention using chemotherapeutic agent gemcitabine with anti-angiogenic peptide vaccination targeting VRGFR1 should be determined in case of advanced/inoperable or therapy-resistant pancreatic cancer patients.

Gemcitabine 1,000mg/m2 BSA will be administered on day1, day8, day15, day29, day36, day43, respectively.

HLA-A*2402-restricted VEGFR1-derived peptide (VEGFR1-A24-1084; SYGVLLWEI) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8weeks (total 16 doses).

Condition	Intervention	Phase
Pancreatic Cancer Pancreas Neoplasms Cancer of Pancreas Neoplasms, Pancreatic Pancreas Cancer	Biological: VEGFR1-A24-1084 (SYGVLLWEI)	Phase I Phase II

MedlinePlus related topics:

Cancer Pancreatic Cancer

ChemIDplus related topics:

Gemcitabine hydrochloride Gemcitabine Montanide ISA 51 Pancrelipase Ultrase

U.S. FDA Resources

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*2402-Restricted Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Derived Peptide Vaccination Combined With Gemcitabine for Advanced Pancreatic Cancer

Further study details as provided by Tokyo University:

Primary Outcome Measures:

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

Secondary Outcome Measures:

Immune response (ELISPOT, Perforin/FoxP3 FACS, in vitro CTL assay etc.) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Tumor regression(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	Biological: VEGFR1-A24-1084 (SYGVLLWEI) HLA-A*2402-restricted VEGFR1-derived peptide (VEGFR1-A24-1084) 1mg emulsified with Montanide ISA51 will be subcutaneously injected 2 times weekly for total 16doses concurrently with conventional dose of gemcitabine 1,000mg/m2 BSA on 1st, 2nd, 3rd, 5th, 6th, 7th weeks for advanced/inoperable pancreatic cancer patients.

Detailed Description:

HLA-A*2402-restricted cytotoxic T lymphocyte (CTL) clones were obtained from healthy volunteer donor peripheral blood.

These CTL clones showed potent cytotoxicities selectively against VEGFR1-expressing target cells in HLA-class I-restricted manner.

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*2402 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: NCT00683358

Contacts


Contact: Hitomi Nagayama, MD,PhD	81-3-5449-5772 ext 75185	zephyrus@ims.u-tokyo.ac.jp

Contact: Nagayama

Locations


Japan, Tokyo
	Research Hospital, The Institute of Medical Science, The University of Tokyo	Recruiting
	Minato-ku, Tokyo, Japan, 108-8639
	Principal Investigator: Hitomi Nagayama, MD,PhD

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

Related Info This link exits the ClinicalTrials.gov site

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.

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.

Responsible Party:	Research Hospital, Institute of Medical Science, The University of Tokyo ( Naohide Yamashita MD, PhD )
Study ID Numbers:	IMSUT-PPKVEGFR12402
First Received:	May 16, 2008
Last Updated:	May 22, 2008
ClinicalTrials.gov Identifier:	NCT00683358
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

Study placed in the following topic categories:

Digestive System Diseases

Digestive System Neoplasms

Pancreatic Neoplasms

Endocrine System Diseases

Pancreatic Diseases

Gastrointestinal Neoplasms

Endocrinopathy

Endothelial Growth Factors

Gemcitabine

Pancrelipase

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 August 29, 2008

Sponsors and Collaborators:	Tokyo University Human Genome Center, Institute of Medical Science, University of Tokyo
Information provided by:	Tokyo University
ClinicalTrials.gov Identifier:	NCT00683358