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

Sponsor

Tokyo University (Other)

Overall Status

Completed

CT.gov ID

NCT00681577

Collaborator

Human Genome Center, Institute of Medical Science, University of Tokyo (Other)

Enrollment

Location

Arm

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Biological: URLC10, KOC1, VEGFR1 and VEGFR2	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

May 1, 2008

Actual Primary Completion Date :

Oct 1, 2009

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	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.

Arm

Intervention/Treatment

Experimental: A

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.

Outcome Measures

Primary Outcome Measures

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

To evaluate immunological responses [two months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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