Pancreatic Cancer
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALVEGFR2-169 and gemcitabine
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.
Sponsors
Human Genome Center, Institute of Medical Science, University of Tokyo
Wakayama Medical 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
DISEASE CHARACTERISTICS 1. locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer 2. measurable disease by CT scan PATIENT CHARACTERISTICS 1. ECOG performance status 0-2 2. Life expectancy \> 3 months 3. 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 4. HLA-A\*2402 5. Able and willing to give valid written informed consent
Exclusion criteria
1. Pregnancy(woman of childbearing potential:Refusal or inability to use effective means of contraception) 2. Breastfeeding 3. Active or uncontrolled infection 4. Concurrent treatment with steroids or immunosuppressing agent 5. Prior chemotherapy of gemcitabine 6. Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks 7. Serious or nonhealing wound, ulcer, or bone fracture 8. Active or uncontrolled other malignancy 9. Ileus 10. Interstitial pneumonia 11. Decision of unsuitableness by principal investigator or physician-in-charge
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety(toxicities as assessed by NCI CTCAE version 3) | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| DTH to VEGFR2 peptide | 3 months |
| Changes in levels of regulatory T cells | 3 months |
| VEGFR2 peptide specific CTL induction in vitro | 3 months |
| Time to progression | 1 years |
| survival | 1 years |
| Objective response rate as assessed by RECIST criteria | 1 year |
Countries
Japan
Outcome results
None listed