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

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

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.

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.

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