Human Leukocyte Antigen-A*02:01-restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer
Primary Purpose
Pancreatic Cancer, Pancreas Neoplasms
Status
Terminated
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
HLA-A*02:01-restricted VEGFR1-derived peptide vaccination
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer focused on measuring cancer, pancreas, advanced, peptide, vaccination, VEGFR1, HLA, gemcitabine, IFA, Cancer of Pancreas, Neoplasms, Pancreas, Pancreas Cancer
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
Sites / Locations
- Research Hospital, The Institute of Medical Science, The University of Tokyo
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Peptide vaccination
Arm Description
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 safety and efficacy of this type of peptide.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00683085
First Posted
May 16, 2008
Last Updated
July 20, 2011
Sponsor
Tokyo University
Collaborators
Human Genome Center, Institute of Medical Science, University of Tokyo
1. Study Identification
Unique Protocol Identification Number
NCT00683085
Brief Title
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
2. Study Status
Record Verification Date
July 2011
Overall Recruitment Status
Terminated
Why Stopped
Lack of eligible patient
Study Start Date
May 2008 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Tokyo University
Collaborators
Human Genome Center, Institute of Medical Science, University of Tokyo
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Pancreas Neoplasms
Keywords
cancer, pancreas, advanced, peptide, vaccination, VEGFR1, HLA, gemcitabine, IFA, Cancer of Pancreas, Neoplasms, Pancreas, Pancreas Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Peptide vaccination
Arm Type
Experimental
Arm Description
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 safety and efficacy of this type of peptide.
Intervention Type
Biological
Intervention Name(s)
HLA-A*02:01-restricted VEGFR1-derived peptide vaccination
Other Intervention Name(s)
VEGFR1-A2-770; TLFWLLLTL
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events
Description
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 Outcome Measure Information:
Title
Number of Participants With Tumor Regression
Description
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.
Time Frame
2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naohide Yamashita, MD, PhD
Organizational Affiliation
Director, Research Hospital, Institute of Medical Science, Tokyo University
Official's Role
Study Director
Facility Information:
Facility Name
Research Hospital, The Institute of Medical Science, The University of Tokyo
City
Minato-ku
State/Province
Tokyo
ZIP/Postal Code
108-8639
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
14512794
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.
Results Reference
background
PubMed Identifier
17020992
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.
Results Reference
background
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Human Leukocyte Antigen-A*02:01-restricted Tumor Vessel Specific Peptide Vaccination for Advanced Pancreatic Cancer
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