Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer

Tracking Information
First Submitted Date ICMJE	February 13, 2008
First Posted Date ICMJE	February 25, 2008
Last Update Posted Date	February 18, 2009
Study Start Date ICMJE	November 2006
Actual Primary Completion Date	December 2006 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 13, 2008)	Safety(toxicities as assessed by NCI CTCAE version 3) [ Time Frame: 3 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00622622 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 13, 2008)	VEGFR2 peptide specific CTL induction in vitro [ Time Frame: 3 months ]; DTH to VEGFR2 peptide [ Time Frame: 3 months ]; Changes in levels of regulatory T cells [ Time Frame: 3 months ]; Objective response rate as assessed by RECIST criteria [ Time Frame: 1 year ]; Time to progression [ Time Frame: 1 years ]; survival [ Time Frame: 1 years ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Gemcitabine With Antiangiogenic Peptide Vaccine Therapy in Patients With Pancreatic Cancer
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Pancreatic Cancer
Intervention ICMJE	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.
Study Arms	Experimental: Phase I study; Intervention: Biological: VEGFR2-169 and gemcitabine
Publications *	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.; 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.; 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.; 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].; 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.; Miyazawa M, Ohsawa R, Tsunoda T, Hirono S, Kawai M, Tani M, Nakamura Y, Yamaue H. Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci. 2010 Feb;101(2):433-9. doi: 10.1111/j.1349-7006.2009.01416.x. Epub 2009 Oct 27.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: February 17, 2009)	21
Original Estimated Enrollment ICMJE; (submitted: February 13, 2008)	18
Actual Study Completion Date	February 2009
Actual Primary Completion Date	December 2006 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	20 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Japan
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00622622
Other Study ID Numbers ICMJE	WPR2-0710
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Second Department of Surgery, Wakayama Medical University
Study Sponsor ICMJE	Wakayama Medical University
Collaborators ICMJE	Human Genome Center, Institute of Medical Science, University of Tokyo
Investigators ICMJE	Study Chair: Hiroki Yamaue, MD Wakayama Medical University, Second Department of Surgery
PRS Account	Wakayama Medical University
Verification Date	February 2009
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP