Human Leukocyte Antigen-A*0201-Restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer

Condition(s) targeted: Pancreatic Cancer; Pancreas Neoplasms; Cancer of Pancreas; Neoplasms, Pancreas; Pancreas Cancer

Intervention: VEGFR1-A02-770 (TLFWLLLTL) (Biological)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Tokyo University

Official(s) and/or principal investigator(s):
Naohide Yamashita, MD, PhD, Study Director, Affiliation: Director, Research Hospital, Institute of Medical Science, Tokyo University

Overall contact:
Hitomi Nagayama, MD,PhD, Phone: 81-3-5449-5772, Ext: 75185, Email: zephyrus@ims.u-tokyo.ac.jp

Feasibility and efficacy of combined modality intervention using conventional dose of gemcitabine with anti-angiogenic peptide vaccination targeting tumor-vessel specific VEGFR1 should be determined in case of advanced/inoperable or therapy-resistant pancreatic cancer patients.

Gemcitabine 1,000mg/m2 (body surface area) will be administered on day 1, day 8, day 15, day 29, day 36, and day 43, respectively.

VEGFR1-derived HLA-A*0201-restricted peptide (VEGFR1-A02-770; TLFWLLLTL) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8 weeks (total 16 doses).

Official title: Phase Ⅰ/Ⅱ Trial of Human Leukocyte Antigen (HLA)-A*0201-Restricted Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Derived Peptide Vaccination Combined With Conventional Dose of Gemcitabine for Advanced Pancreatic Cancer

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Phase 1; safety (NCI CTCAE v.3) Phase 2; time to progression (RECIST)

Secondary outcome:

Immune response (ELISPOT, FACS for perforin/FOXP3, in vitro CTL assay, etc.)

Tumor regression (RECIST by imaging study, tumor marker, etc.)

Detailed description: HLA-A*0201-restricted VEGFR1-specific cytotoxic T lymphocyte (CTL) responses were obtained from HLA-A2/Kd transgenic murine model.

HLA-A*0201-restricted VEGFR1-specific CTL clones were also obtained from peripheral blood mononuclear cells of healthy volunteer donors.

These CTL clones showed potent anti-tumor CTL responses in HLA class Ⅰ-restricted manner in vitro.

Vaccination of HLA-A*0201-restricted VEGFR1-specific peptide to A2/Kd transgenic mice markedly suppress the tumor-induced angiogenesis and tumor growth in vivo.

Minimum age: 20 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Heterozygote or homozygote of HLA-A*0201 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/μL100,000/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

Hitomi Nagayama, MD,PhD, Phone: 81-3-5449-5772, Ext: 75185, Email: zephyrus@ims.u-tokyo.ac.jp

Research Hospital, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Recruiting
Hitomi Nagayama, MD,PhD, Principal Investigator

Related publications:

Nagayama H, Sato K, Morishita M, Uchimaru K, Oyaizu N, Inazawa T, Yamasaki T, Enomoto M, Nakaoka T, Nakamura T, Maekawa T, Yamamoto A, Shimada S, Saida T, Kawakami Y, Asano S, Tani K, Takahashi TA, Yamashita N. Results of a phase I clinical study using autologous tumour lysate-pulsed monocyte-derived mature dendritic cell vaccinations for stage IV malignant melanoma patients combined with low dose interleukin-2. Melanoma Res. 2003 Oct;13(5):521-30.

Ishizaki H, Tsunoda T, Wada S, Yamauchi M, Shibuya M, Tahara H. Inhibition of tumor growth with antiangiogenic cancer vaccine using epitope peptides derived from human vascular endothelial growth factor receptor 1. Clin Cancer Res. 2006 Oct 1;12(19):5841-9.

Starting date: May 2008
Ending date: April 2009
Last updated: May 22, 2008