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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Gastric Cancer

Intervention / Treatment
-----------------
* Biological: URLC10, VEGFR1 and VEGFR2


Participation Criteria
=================
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*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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Biological: URLC10, VEGFR1 and VEGFR2<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate immunological responses |  | two months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peptide Vaccine, URLC10, VEGFR1, VEGFR2