Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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-A2402 in vitro, and this peptide induces CTL from cancer patients. 60% in Japanese population have HLA-A2402. 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase I study
|
Biological: VEGFR2-169 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.
|
Outcome Measures
Primary Outcome Measures
- Safety(toxicities as assessed by NCI CTCAE version 3) [3 months]
Secondary Outcome Measures
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
DISEASE CHARACTERISTICS
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locally advanced or metastatic pancreatic cancer precluding curative surgical resection and recurrent pancreatic cancer
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measurable disease by CT scan
PATIENT CHARACTERISTICS
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ECOG performance status 0-2
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Life expectancy > 3 months
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Laboratory values as follows
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2000/mm3 < WBC < 15000/mm3
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Platelet count > 75000/mm3
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Bilirubin < 3.0 mg/dl
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Aspartate transaminase < 150 IU/L
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Alanine transaminase < 150 IU/L
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Creatinine < 3.0 mg/dl
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HLA-A*2402
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Able and willing to give valid written informed consent
Exclusion Criteria:
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Pregnancy(woman of childbearing potential:Refusal or inability to use effective means of contraception)
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Breastfeeding
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Active or uncontrolled infection
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Concurrent treatment with steroids or immunosuppressing agent
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Prior chemotherapy of gemcitabine
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Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks
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Serious or nonhealing wound, ulcer, or bone fracture
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Active or uncontrolled other malignancy
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Ileus
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Interstitial pneumonia
-
Decision of unsuitableness by principal investigator or physician-in-charge
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Wakayama Medical University Hospital | 811-1 Kimiidera, Wakayama | Wakayama | Japan |
Sponsors and Collaborators
- Wakayama Medical University
- Human Genome Center, Institute of Medical Science, University of Tokyo
Investigators
- Study Chair: Hiroki Yamaue, MD, Wakayama Medical University, Second Department of Surgery
Study Documents (Full-Text)
None provided.More Information
Publications
- Correale P, Cusi MG, Del Vecchio MT, Aquino A, Prete SP, Tsang KY, Micheli L, Nencini C, La Placa M, Montagnani F, Terrosi C, Caraglia M, Formica V, Giorgi G, Bonmassar E, Francini G. Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro. J Immunol. 2005 Jul 15;175(2):820-8. Erratum in: J Immunol. 2005 Nov 1;175(9):6235. Prete, Salvatore [corrected to Prete, Salvatore Pasquale].
- Date Y, Kimura A, Kato H, Sasazuki T. DNA typing of the HLA-A gene: population study and identification of four new alleles in Japanese. Tissue Antigens. 1996 Feb;47(2):93-101.
- Dauer M, Herten J, Bauer C, Renner F, Schad K, Schnurr M, Endres S, Eigler A. Chemosensitization of pancreatic carcinoma cells to enhance T cell-mediated cytotoxicity induced by tumor lysate-pulsed dendritic cells. J Immunother. 2005 Jul-Aug;28(4):332-42.
- Li Y, Wang MN, Li H, King KD, Bassi R, Sun H, Santiago A, Hooper AT, Bohlen P, Hicklin DJ. Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. J Exp Med. 2002 Jun 17;195(12):1575-84. Erratum in: J Exp Med 2002 Aug 19;196(4):557.
- Niethammer AG, Xiang R, Becker JC, Wodrich H, Pertl U, Karsten G, Eliceiri BP, Reisfeld RA. A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med. 2002 Dec;8(12):1369-75. Epub 2002 Nov 4.
- Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M, Tahara H. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005 Jun 1;65(11):4939-46.
- WPR2-0710