Histocompatibility Leukocyte Antigen (HLA)-A*0201 Restricted Peptide Vaccine Therapy in Patients With Gastric Cancer

Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*0201 in Treating Patients With Refractory Gastric Cancer

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.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Biological: URLC10, VEGFR1 and VEGFR2

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 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 URLC10-117 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.

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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*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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 in combination with S-1 chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety (Phase I: toxicities as assessed by NCI CTCAE version 3) and efficacy (Phase II: Feasibility as evaluated by RECIST)	two months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate immunological responses	two months

Collaborators and Investigators

• Sponsor: Tokyo University
• Collaborators: Human Genome Center, Institute of Medical Science, University of Tokyo

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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. doi: 10.1038/sj.onc.1205755.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: May 19, 2008
• First Submitted That Met QC Criteria: May 19, 2008
• First Posted (Estimate): May 21, 2008

Study Record Updates

• Last Update Posted (Estimate): November 19, 2009
• Last Update Submitted That Met QC Criteria: November 18, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: Peptide Vaccine; VEGFR1; VEGFR2; URLC10
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: IMS-MKA0201