Histocompatibility Leukocyte Antigen (HLA)-A*2402 Restricted Peptide Vaccine Therapy in Patients With Esophageal Cancer
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, TTK, and KOC1, emulsified with Montanide ISA 51.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST) [Two months]
Secondary Outcome Measures
- To evaluate immunological responses [Two months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Advanced or recurrent esophageal cancer
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Resistant against conventional chemotherapy or difficult to continue the chemotherapy due to intolerable side effect(s)
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ECOG performance status 0-2
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Life expectancy > 3 months
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HLA-A*2402
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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
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Able and willing to give valid written informed consent
Exclusion Criteria:
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Pregnancy (woman of childbearing potential:Refusal or inability to use effective means of contraception)
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Breastfeeding
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Active or uncontrolled infection
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Concurrent treatment with steroids or immunosuppressing agent
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Prior chemotherapy, radiation therapy, and/or immunotherapy within 4 weeks
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Uncontrolled brain and/or intraspinal metastasis
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Decision of unsuitableness by principal investigator or physician-in-charge
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Institutute of Medical Science, University of Tokyo | 4-6-1, Shirokanedai, Minato-ku | Tokyo | Japan | 108-8639 |
Sponsors and Collaborators
- Tokyo University
- 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
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- IMS-OKA2402