Histocompatibility Leukocyte Antigen (HLA)-A*2402 Restricted Peptide Vaccine Therapy in Patients With Gastric Cancer

NCT ID: NCT00681577

Last Updated: 2009-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2009-10-31

Brief Summary

The purpose of this study is to evaluate the safety and time to progression of HLA-A*2402 restricted epitope peptides URLC10, KOC1, VEGFR1 and VEGFR2 emulsified with Montanide ISA 51.

Detailed Description

URLC10 and KOC1 have 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 and KOC1 are upregulated in human gastric 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 peptide (1mg), KOC1 peptide (1mg), VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. The patients will also receive oral chemotherapy (S-1) simultaneously. 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.

Conditions

Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Group Type: EXPERIMENTAL

URLC10, KOC1, VEGFR1 and VEGFR2

Intervention Type: BIOLOGICAL

Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, the URLC10 peptide (1mg), KOC1 peptide (1mg), VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection in combination with S-1 chemotherapy.

Interventions

URLC10, KOC1, VEGFR1 and VEGFR2

Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, the URLC10 peptide (1mg), KOC1 peptide (1mg), VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection in combination with S-1 chemotherapy.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Advanced or recurrent gastric 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*2402
• 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 to receive oral TS-1 therapy
• 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
• History of allergy to Tegaful, Gimeracil and/or Oteracil
• Decision of unsuitableness by principal investigator or physician-in-charge

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: collaborator

Tokyo University

OTHER

Sponsor Role: lead

Responsible Party

The Institute of Medical Science, The University of Tokyo

Principal Investigators

Naohide Yamashita, MD/PhD

Role: STUDY_CHAIR

Tokyo University

Locations

The Institutute of Medical Science, University of Tokyo

4-6-1, Shirokanedai, Minato-ku, Tokyo, Japan

Countries

Japan

References

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.

Reference Type: BACKGROUND

PMID: 11280777 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12460921 (View on PubMed)

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. doi: 10.1158/1078-0432.CCR-06-0750.

Reference Type: BACKGROUND

PMID: 17020992 (View on PubMed)

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. doi: 10.1158/0008-5472.CAN-04-3759.

Reference Type: BACKGROUND

PMID: 15930316 (View on PubMed)

Lin YM, Furukawa Y, Tsunoda T, Yue CT, Yang KC, Nakamura Y. Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas. Oncogene. 2002 Jun 13;21(26):4120-8. doi: 10.1038/sj.onc.1205518.

Reference Type: BACKGROUND

PMID: 12037668 (View on PubMed)

Other Identifiers

IMS-MKA2402

Identifier Type: -

Identifier Source: org_study_id