Histocompatibility Leukocyte Antigen (HLA)-A*0201 Restricted Peptide Vaccine Therapy in Patients With Esophageal Cancer - Full Text View

Purpose

The purpose of this study is to evaluate the safety and time to progression of HLA-A*0201 restricted epitope peptides URLC10, VEGFR1 and VEGFR2 emulsified with Montanide ISA 51.

Condition	Intervention	Phase
Esophageal Cancer	Biological: URLC10, VEGFR1 and VEGFR2	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*0201 in Treating Patients With Refractory Esophageal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

U.S. FDA Resources

Further study details as provided by Tokyo University:

Primary Outcome Measures:

Safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST) [ Time Frame: two months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate immunological responses [ Time Frame: two months ] [ Designated as safety issue: No ]

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

Arms	Assigned Interventions
Experimental: A	Biological: URLC10, VEGFR1 and VEGFR2 Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, the URLC10 peptide (1mg), VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection.

Detailed Description:

URLC10 has been identified as cancer specific molecules especially in non small cell lung cancer using genome-wide expression profile analysis by cDNA microarray technique. In a prior study, it has been shown that URLC10 is upregulated in human esophageal tumors. VEGF receptor 1 and 2 are essential targets to tumor angiogenesis, and we identified that peptides derived from these receptors significantly induce the effective tumor specific CTL response in vitro and vivo. According to these findings, in this trial, we evaluate the safety, immunological and clinical response of those peptides. Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, the URLC10-117 peptide(1mg), VEGFR1 peptide(1mg) and VEGFR2 peptide(1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. Repeated cycles of vaccine will be administered until patients develop progressive disease or unacceptable toxicity, whichever occurs first. In the phase I study, we evaluate the safety and tolerability of these peptide vaccines. In the following phase II study, we evaluate the immunological and clinical response of this vaccine therapy.

Eligibility

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

Criteria

Inclusion Criteria:

Advanced or recurrent esophageal cancer
Resistant against conventional chemotherapy or difficult to continue the chemotherapy due to intolerable side effect(s)
ECOG performance status 0-2
Life expectancy > 3 months
HLA-A*0201
Laboratory values as follows 2000/mm3<WBC<15000/mm3 Platelet count>100000/mm3 Bilirubin < 3.0mg/dl Asparate transaminase < 150IU/L Alanine transaminase < 150IU/L Creatinine < 3.0mg/dl
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
Unhealed external wound
Concurrent treatment with steroids or immunosuppressing agent
Prior chemotherapy, radiation therapy, and/or immunotherapy within 4 weeks
Uncontrolled brain and/or intraspinal metastasis
Decision of unsuitableness by principal investigator or physician-in-charge

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00681421

Locations

Japan
The Institutute of Medical Science, University of Tokyo
4-6-1, Shirokanedai, Minato-ku, Tokyo, Japan, 108-8639

Sponsors and Collaborators

Tokyo University

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

Investigators

Study Chair:

Naohide Yamashita, MD/PhD

The Institute of Medical Science, The University of Tokyo

More Information

Publications:

Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y, Nakamura Y. Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res. 2001 Mar 1;61(5):2129-37.

Hasegawa S, Furukawa Y, Li M, Satoh S, Kato T, Watanabe T, Katagiri T, Tsunoda T, Yamaoka Y, Nakamura Y. Genome-wide analysis of gene expression in intestinal-type gastric cancers using a complementary DNA microarray representing 23,040 genes. Cancer Res. 2002 Dec 1;62(23):7012-7.

Takahashi M, Tsunoda T, Seiki M, Nakamura Y, Furukawa Y. Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene. 2002 Aug 29;21(38):5861-7.

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.

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.

Responsible Party:	Naohida Yamashita, MD/PhD, The Institute of Medical Science, The University of Tokyo
ClinicalTrials.gov Identifier:	NCT00681421 History of Changes
Other Study ID Numbers:	IMS-OKA0201
Study First Received:	May 19, 2008
Last Updated:	November 18, 2009
Health Authority:	Japan: Institutional Review Board

Keywords provided by Tokyo University:

Peptide Vaccine
URLC10
VEGFR1
VEGFR2

Additional relevant MeSH terms:

Esophageal Diseases
Esophageal Neoplasms
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms

Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms

ClinicalTrials.gov processed this record on May 23, 2013