Combination of Chemoradiation Therapy and Epitope Peptide Vaccine Therapy in Treating Patients With Esophageal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immune response of multiple peptides (URLC10, TTK, KOC1 VEGFR1, and VEGFR2) emulsified with Montanide ISA51 in combination with chemotherapy (CDDP, 5-FU) plus radiation therapy in treating patients with unresectable, advanced or recurrent esophageal cancer.

Detailed Description
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Up-regulated ling cancer 10 (URLC10), TTK protein kinase (TTK) and K homology domain containing protein over expressed in cancer (KOC1) were identified as new targets of tumor associated antigens using cDNA microarray technologies combined with the expression profiles of normal and cancer tissues. Furthermore, anti-angiogenic therapy is now considered to be one of promising approaches for treating cancer. Vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2) are essential targets for tumor angiogenesis. Epitope peptides for these targets are able to induce cytotoxic T lymphocytes (CTL) restricted to HLA-A *2402 in vivo. On the other hand, chemotherapy (CDDP, 5-FU) plus radiation therapy has been to be a standard treatment for unresectable advanced esophageal cancer. In this clinical trial, we evaluate the safety and immune responses of different doses of multiple peptides (URLC10, TTK, KOC1, VEGFR1, and VEGFR 2) emulsified with Montanide ISA 51 in combination with chemotherapy (CDDP, 5-FU) plus radiation therapy in treating patients with unresectable, advanced or recurrent esophageal cancer.

Official Title
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Phase I Study of Chemoradiation Therapy With Epitope Peptide Vaccine Therapy in Treating Patients With Unresectable, Advanced or Recurrent Esophageal Cancer

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Biological: URLC10, TTK, KOC1, VEGFR1, VEGFR2, cisplatin, fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have unresectable, locally advanced, recurrent or metastatic disease of esophageal cancer. measurable disease by CT scan ECOG performance status of 0 to 2 Expected survival of at lease 3months Patients must be HLA-A2402 Laboratory values as follow: WBC > 2000/mm3, Platelet count > 75000/mm3, Total bilirubin < 1.5 x the institutional normal upper limits, Creatinine < 1.5 x the institutional normal upper limits, AST. ALT. ALP < 2.5 x the institutional normal upper limits Able and willing to give valid written informed consent Exclusion Criteria: Pregnancy (women of childbearing potential:Refusal or inability to use effective means of contraception) Breastfeeding Active or uncontrolled infection Prior chemotherapy,radiation therapy or immunotherapy within 4 weeks Concurrent treatment with steroid or immunosuppressing agent Patient with peptic ulcer disease Active or uncontrolled other malignancy Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ Disease to the central nervous system Decision of unsuitableness by principal investigator or physician-in-charge

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: URLC10, TTK, KOC1, VEGFR1, VEGFR2, cisplatin, fluorouracil<br>* Escalating dose of multiple peptides (URLC10, TTK, KOC1 VEGFR1, and VEGFR2) emulsified with Montanide ISA51 will be administered by subcutaneous injection on days 15, 22, 28 and 35 of treatment cycle. Doses of each peptide are planning 0.5mg, 1mg and 3mg/body. Chemotherapy plus radiation therapy will be done as follows: fluorouracil (400mg/m2) on day1-5 and 8-12, cisplatin (40mg/m2) on days 1 and 8, radiation (2Gy) on days 1-5, 8-12 and 15-19. Two cycles of combination of chemoradiation therapy and epitope peptide vaccine therapy will be done.<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety(toxicities as assessed by NCI CTCAE version3) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peptide specific CTL induction |  | 3 months | 
| DTH to peptide |  | 3 months | 
| Changes in levels of regulatory T cells |  | 3 months | 
| Objective response rate as assessed by RECIST criteria |  | 1 year | 
| Time to progression |  | 1 year | 
| survival |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epitope peptide, Vaccination, Chemoradiation, Esophageal cancer