Esophageal Cancer
Conditions
Keywords
Epitope peptide, Vaccination, Chemoradiation, Esophageal cancer
Brief summary
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
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.
Interventions
BIOLOGICALURLC10, TTK, KOC1, VEGFR1, VEGFR2, cisplatin, fluorouracil
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.
Sponsors
Human Genome Center, Institute of Medical Science, University of Tokyo
Teikyo University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients must have unresectable, locally advanced, recurrent or metastatic disease of esophageal cancer. 2. measurable disease by CT scan 3. ECOG performance status of 0 to 2 4. Expected survival of at lease 3months 5. Patients must be HLA-A2402 6. 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 7. Able and willing to give valid written informed consent
Exclusion criteria
1. Pregnancy (women of childbearing potential:Refusal or inability to use effective means of contraception) 2. Breastfeeding 3. Active or uncontrolled infection 4. Prior chemotherapy,radiation therapy or immunotherapy within 4 weeks 5. Concurrent treatment with steroid or immunosuppressing agent 6. Patient with peptic ulcer disease 7. Active or uncontrolled other malignancy 8. Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ 9. Disease to the central nervous system 10. Decision of unsuitableness by principal investigator or physician-in-charge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety(toxicities as assessed by NCI CTCAE version3) | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| DTH to peptide | 3 months |
| Changes in levels of regulatory T cells | 3 months |
| Peptide specific CTL induction | 3 months |
| Time to progression | 1 year |
| survival | 1 year |
| Objective response rate as assessed by RECIST criteria | 1 year |
Countries
Japan
Contacts
Primary ContactHisae Iinuma, PhD
Outcome results
None listed