Human Leukocyte Antigen-A*2402-Restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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Feasibility and efficacy of combined modality intervention using chemotherapeutic agent gemcitabine with anti-angiogenic peptide vaccination targeting VRGFR1 should be determined in case of advanced/inoperable or therapy-resistant pancreatic cancer patients. Gemcitabine 1,000mg/m2 BSA will be administered on day1, day8, day15, day29, day36, day43, respectively. HLA-A*2402-restricted VEGFR1-derived peptide (VEGFR1-A24-1084; SYGVLLWEI) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8weeks (total 16 doses).

Detailed Description
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HLA-A*2402-restricted cytotoxic T lymphocyte (CTL) clones were obtained from healthy volunteer donor peripheral blood. These CTL clones showed potent cytotoxicities selectively against VEGFR1-expressing target cells in HLA-class I-restricted manner.

Official Title
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Phase Ⅰ/Ⅱ Trial of Human Leukocyte Antigen (HLA)-A*2402-Restricted Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Derived Peptide Vaccination Combined With Gemcitabine for Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer, Pancreas Neoplasms

Intervention / Treatment
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* Biological: VEGFR1-A24-1084 (SYGVLLWEI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heterozygote or homozygote of HLA-A*2402 allele Inoperable or recurrent pancreatic cancer with or without any prior therapy Difficult to continue the prior therapy due to treatment-related toxicities ECOG performance status 0-2 Evaluable primary or metastatic lesion with RECIST criteria Clearance period from prior therapy more than 4 weeks Life expectancy more than 3 months Laboratory values as follows 2,000/μL<WBC<15,000/μL Platelet count>100,000/μL AST<150IU/L ALT<150IU/L Total bilirubin<3.0mg/dl Serum creatinine<3.0mg/dl Exclusion Criteria: Pregnancy (refusal or inability to use effective contraceptives) Breastfeeding Active or uncontrolled infection Systemic use of corticosteroids or immunosuppressants Uncontrollable brain metastasis and/or meningeal infiltration Unhealed external wound Possibilities of complicated paralytic ileus or interstitial pneumonitis Decision of not eligible determined by principal investigator or attending doctor

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: VEGFR1-A24-1084 (SYGVLLWEI)<br>* HLA-A*2402-restricted VEGFR1-derived peptide (VEGFR1-A24-1084) 1mg emulsified with Montanide ISA51 will be subcutaneously injected 2 times weekly for total 16doses concurrently with conventional dose of gemcitabine 1,000mg/m2 BSA on 1st, 2nd, 3rd, 5th, 6th, 7th weeks for advanced/inoperable pancreatic cancer patients.<br>* Other names: Montanide ISA51;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PhaseⅠ; safety (NCI CTCAE v.3) PhaseⅡ；time to progression (RECIST) |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response (ELISPOT, Perforin/FoxP3 FACS, in vitro CTL assay etc.) |  | 1 year | 
| Tumor regression(Imaging study, tumor marker, etc.) |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, pancreas, advanced, peptide, vaccination, VEGFR1, HLA, gemcitabine, IFA, Cancer of Pancreas, Neoplasms, Pancreatic, Pancreas Cancer