Clinical trial NCT00683358: Human Leukocyte Antigen-A*2402-Restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer
Official title: Phase Ⅰ/Ⅱ Trial of Human Leukocyte Antigen (HLA)-A*2402-Restricted Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Derived Peptide Vaccination Combined With Gemcitabine for Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Pancreas Neoplasms
Keywords: cancer
pancreas
advanced
peptide
vaccination
VEGFR1
HLA
gemcitabine
IFA
Cancer of Pancreas
Neoplasms, Pancreatic
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: 14
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: Feasibility and efficacy of combined modality intervention using chemotherapeutic agent gemcitabine with anti-angiogenic peptide vaccination targeting VRGFR1 should be determined in case of advanced/inoperable or therapy-resistant pancreatic cancer patients.

Gemcitabine 1,000mg/m2 BSA will be administered on day1, day8, day15, day29, day36, day43, respectively.

HLA-A\*2402-restricted VEGFR1-derived peptide (VEGFR1-A24-1084; SYGVLLWEI) emulsified with Montanide ISA51 will be subcutaneously injected twice weekly for 8weeks (total 16 doses).

Detailed description: HLA-A\*2402-restricted cytotoxic T lymphocyte (CTL) clones were obtained from healthy volunteer donor peripheral blood.

These CTL clones showed potent cytotoxicities selectively against VEGFR1-expressing target cells in HLA-class I-restricted manner.

Eligibility criteria: Inclusion Criteria:

* Heterozygote or homozygote of HLA-A\*2402 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/μL\<WBC\<15,000/μL Platelet count\>100,000/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

Primary outcomes:
measure: PhaseⅠ; safety (NCI CTCAE v.3) PhaseⅡ；time to progression (RECIST)
timeFrame: 1 year
Secondary outcomes:
measure: Immune response (ELISPOT, Perforin/FoxP3 FACS, in vitro CTL assay etc.)
timeFrame: 1 year
measure: Tumor regression(Imaging study, tumor marker, etc.)
timeFrame: 1 year
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: 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.
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.