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

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00683085
• Other study ID #: IMSUT-PPKVEGFR10201
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: May 16, 2008
• Last updated: July 20, 2011
• Start date: May 2008
• Est. completion date: May 2009

Study information

• Verified date: July 2011
• Source: Tokyo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Education, Culture, Sports, Science and Technology
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 85 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreas Neoplasms
• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• HLA-A*02:01-restricted VEGFR1-derived peptide vaccination
VEGFR1-derived HLA-A*02:01-restricted peptide (VEGFR1-A2-770; TLFWLLLTL)was vaccinated twice weekly for 8 weeks (total 16 doses) combined with conventional dose (1,000 mg/m^2 body surface area) of gemcitabine 6 doses for advanced stage pancreatic cancer to confirm the feasibility and efficacy of this type of peptide.

Locations

Country	Name	City	State
Japan	Research Hospital, The Institute of Medical Science, The University of Tokyo	Minato-ku	Tokyo

Sponsors (2)

Lead Sponsor	Collaborator
Tokyo University	Human Genome Center, Institute of Medical Science, University of Tokyo

Country where clinical trial is conducted

Japan, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	2 months	Yes
Secondary	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.	2 months	No