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

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

The purpose of this study is to evaluate the safety and time to progression of HLA-A*2402 restricted epitope peptides URLC10, TTK, and KOC1, emulsified with Montanide ISA 51.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer
• Intervention / Treatment: Biological: URC10, TTK, KOC1

Detailed Description

URLC10, KOC1 and TTK 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, KOC1 and TTK are upregulated in human esophageal tumors. We identified that peptides derived from these proteins 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), and TTK peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. 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 esophageal 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 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
• Concurrent treatment with steroids or immunosuppressing agent
• Prior chemotherapy, radiation therapy, and/or immunotherapy within 4 weeks
• Uncontrolled brain and/or intraspinal metastasis
• 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: URC10, TTK, KOC1; Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, the URLC10 peptide (1mg), KOC1 peptide (1mg) and TTK peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety(Phase I:toxicities as assessed by NCI CTCAE version3) 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
• Investigators: Study Chair: Naohide Yamashita, MD/PhD, The Institutute of Medical Science, University of Tokyo

Publications and helpful links

General Publications

• 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. doi: 10.1038/sj.onc.1205518.
• 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.
• 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.

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; TTK; URLC10; KOC1
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: IMS-OKA2402