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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and time to progression of HLA-A*2402 restricted epitope peptides RNF43, TOMM34, VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in combination with Tegafur/Uracil/Folinate chemotherapy.

Detailed Description
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RNF43 and TOMM34 have been identified as cancer specific molecules especially in colorectal cancer using genome-wide expression profile analysis by cDNA microarray technique. 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, RNF43 peptide (1mg), TOMM34 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 (Tegafur/Uracil/Folinate) simultaneously. Repeated cycles of the vaccine and the chemotherapy 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 vaccine. In the following phase II study, we evaluate the immunological and clinical response of this vaccine therapy.

Official Title
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Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*2402 in Combination With Tegafur/Uracil/Folinate in Treating Patients With Refractory Colorectal Cancer

Conditions
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Colorectal Cancer, Colon Cancer, Rectal Cancer

Intervention / Treatment
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* Biological: RNF43, TOMM34, VEGFR1 and VEGFR2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced or recurrent colorectal cancer Resistant against chemotherapy including CPT-11, l-OHP、+/- 5-FU +/- bevacizumab 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 Tegafur/Uracil/Folinate 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, or immunotherapy within 4 weeks Uncontrolled brain and/or intraspinal lesion(s) History of allergy to Tegafur, Uracil, and/or Folinate Decision of unsuitableness by principal investigator or physician-in-charge

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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: A<br> | Biological: RNF43, TOMM34, VEGFR1 and VEGFR2<br>* Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, RNF43 peptide (1mg), TOMM34 peptide (1mg), VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection in combination with Tegafur/Uracil/Folinate chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST) |  | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate immunological responses |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HLA-A*2402, Peptide Vaccine, RNF43, TOMM34, VEGFR1, VEGFR2