Clinical trial NCT00683085: Human Leukocyte Antigen-A*02:01-restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer
Official title: Phase I/II Trial of Human Leukocyte Antigen (HLA)-A*02:01-restricted Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Derived Peptide Vaccination Combined With Conventional Dose of Gemcitabine for Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Pancreas Neoplasms
Keywords: cancer
pancreas
advanced
peptide
vaccination
VEGFR1
HLA
gemcitabine
IFA
Cancer of Pancreas
Neoplasms, Pancreas
Pancreas Cancer
Lead sponsor: Tokyo University
Sponsor class: OTHER
Collaborators: name: Human Genome Center, Institute of Medical Science, University of Tokyo
First posted: 2008-05-23
Enrollment: 2
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events
timeFrame: 2 months
Secondary outcomes:
measure: Number of Participants With Tumor Regression
timeFrame: 2 months
Other outcomes:
Locations:
city: Minato-ku
country: Japan
facility: Research Hospital, The Institute of Medical Science, The University of Tokyo
state: Tokyo
Study officials:
affiliation: Director, Research Hospital, Institute of Medical Science, Tokyo University
name: Naohide Yamashita, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1097/00008390-200310000-00011.
citation: 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. doi: 10.1158/1078-0432.CCR-06-0750.