Human Leukocyte Antigen-A*02:01-restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer

Phase 2TerminatedNCT00683085

Tokyo University2 enrolled

Overview

Pancreatic cancer is the fourth leading cause of cancer death in the United States, and no combination therapy is far superior to gemcitabine alone. Vascular endothelial growth factor receptor type 1 (VEGFR1) is expressed on the tumor vessels and a candidate of tumor vessel-specific peptide vaccination strategy to induce T cell immune response. We conducted the study to confirm the safety and efficacy of combined modality intervention using conventional dose of gemcitabine with peptide vaccination targeting tumor-vessel specific VEGFR1 in case of advanced/inoperable or therapy-resistant pancreatic cancer patients. Gemcitabine 1,000 mg/m\^2 (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\*02:01-restricted peptide (VEGFR1-A02-770; TLFWLLLTL) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8 weeks (total 16 doses).

HLA-A\*02:01-restricted VEGFR1-specific cytotoxic T lymphocyte (CTL) responses were obtained from HLA-A2/Kd transgenic murine model. HLA-A\*02:01-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\*02:01-restricted VEGFR1-specific peptide to A2/Kd transgenic mice markedly suppress the tumor-induced angiogenesis and tumor growth in vivo.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pancreatic Cancer

Eligibility

Sex: ALLMin age: 20 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Heterozygote or homozygote of HLA-A\*02:01 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 v.1.0 criteria * Clearance period from prior therapy more than 4 weeks * Life expectancy more than 3 months * Laboratory values as follows 2,000/μL\< WBC \<15,000/μL Platelet count \>100,000/μL AST \<150 IU/L ALT \<150 IU/L Total bilirubin \<3.0 mg/dl Serum creatinine \<3.0 mg/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

Outcomes

Primary Outcomes

Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events

Number of participants without grade 4 hematological or grade 3 other adverse events were caslculated based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI CTCAE v.3)

Time frame: 2 months

Secondary Outcomes

Number of Participants With Tumor Regression

Sum of diameters of primary pancreatic tumor or metastatic tumors (target lesions) before and after vaccination were measured by computed tomography. Sum of tumors' size diameters decrease more than 30% after vaccination was diagnosed as response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines.