Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability and immune response of different doses of VEGFR2-169 emulsified with Montanide ISA 51 in combination with gemcitabine and to determine the recommended phase II dose.

Detailed Description
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Vascular endothelial growth factor receptor 2(VEGFR2) is essential target for tumor angiogenesis, and VEGFR2-169 induces specific Cytotoxic T lymphocytes (CTL) against VEGFR2 expressed targets. VEGFR2-169 shows strong anti-tumor effects restricted to HLA-A*2402 in vitro, and this peptide induces CTL from cancer patients. 60% in Japanese population have HLA-A*2402. VEGFR2-169 is suitable for clinical trial, and gemcitabine has been approved against pancreatic cancer. Gemcitabine is reported to improve immune-response, therefore synergistic effect between vaccine therapy and chemotherapy will be expected. In this clinical trial, we evaluate the safety, tolerability and immune response of different doses of VEGFR2-169 emulsified with Montanide ISA 51 in combination with gemcitabine and to determine the recommended phase II dose of peptide.

Official Title
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Phase I Study of Gemcitabine With Antiangiogenic Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*2402 Derived From VEGFR2 in Patients With Unresectable, Locally Advanced, Recurrent or Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: VEGFR2-169 and gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DISEASE CHARACTERISTICS locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer measurable disease by CT scan PATIENT CHARACTERISTICS ECOG performance status 0-2 Life expectancy > 3 months Laboratory values as follows 2000/mm3 < WBC < 15000/mm3 Platelet count > 75000/mm3 Bilirubin < 3.0 mg/dl Aspartate transaminase < 150 IU/L Alanine transaminase < 150 IU/L Creatinine < 3.0 mg/dl HLA-A*2402 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 Concurrent treatment with steroids or immunosuppressing agent Prior chemotherapy of gemcitabine Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks Serious or nonhealing wound, ulcer, or bone fracture Active or uncontrolled other malignancy Ileus Interstitial pneumonia 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: Phase I study<br> | Biological: VEGFR2-169 and gemcitabine<br>* Escalating doses of VEGFR2-169 will be administered by subcutaneous injection on days 1,8,15 and 22 of each 28-day treatment cycles(doses of 0.5,1.0,2.0mg/body are planned). Gemcitabine will be administered intravenously at a fixed dose of 1000mg/m2 on days 1,8 and 15. Repeated cycles of VEGFR2-169 and gemcitabine will be administered until patients develop progressive disease or unacceptable toxicity,or for maximum 2 cycles, whichever occurs first.<br>|

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 version 3) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VEGFR2 peptide specific CTL induction in vitro |  | 3 months | 
| DTH to VEGFR2 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 years | 
| survival |  | 1 years |