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

Gastric Cancer Clinical Trial

Official title:

Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*2402 in Treating Patients With Refractory Gastric Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00681577
• Other study ID #: IMS-MKA2402
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 19, 2008
• Last updated: November 18, 2009
• Start date: May 2008
• Est. completion date: October 2009

Study information

• Verified date: November 2009
• Source: Tokyo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 85 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
Japan	The Institutute of Medical Science, University of Tokyo	4-6-1, Shirokanedai, Minato-ku	Tokyo

Sponsors (2)

Lead Sponsor	Collaborator
Tokyo University	Human Genome Center, Institute of Medical Science, University of Tokyo

Country where clinical trial is conducted

Japan, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	safety (Phase I: toxicities as assessed by NCI CTCAE version 3) and efficacy (Phase II: Feasibility as evaluated by RECIST)		two months	Yes
Secondary	To evaluate immunological responses		two months	No