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

This study has been terminated.
(Lack of eligible patient)
Sponsor:
Collaborator:
Human Genome Center, Institute of Medical Science, University of Tokyo
Information provided by:
Tokyo University
ClinicalTrials.gov Identifier:
NCT00683085
First received: May 16, 2008
Last updated: July 20, 2011
Last verified: July 2011
History of Changes
  Purpose

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).


Condition Intervention Phase
Pancreatic Cancer
Pancreas Neoplasms
 Biological: HLA-A*02:01-restricted VEGFR1-derived peptide vaccination
 Phase 1
Phase 2

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Tokyo University:

Primary Outcome Measures:
  • Number of Participants Without Grade 4 Hematological or Grade 3 to 4 Non-hematological Adverse Events [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 2
Study Start Date: May 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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 safety and efficacy of this type of peptide.
 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.
Other Name: VEGFR1-A2-770; TLFWLLLTL

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

Ages Eligible for Study:   20 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00683085

Locations
Japan
Research Hospital, The Institute of Medical Science, The University of Tokyo
Minato-ku, Tokyo, Japan, 108-8639
Sponsors and Collaborators
Tokyo University
Human Genome Center, Institute of Medical Science, University of Tokyo
Investigators
Study Director: Naohide Yamashita, MD, PhD Director, Research Hospital, Institute of Medical Science, Tokyo University
  More Information

Publications:

Responsible Party: Naohide Yamashita MD,PhD, Research Hospital, The Institute of Medical Science, The University of Tokyo
ClinicalTrials.gov Identifier: NCT00683085     History of Changes
Other Study ID Numbers: IMSUT-PPKVEGFR10201
Study First Received: May 16, 2008
Results First Received: June 9, 2009
Last Updated: July 20, 2011
Health Authority: Japan: Ministry of Education, Culture, Sports, Science and Technology

Keywords provided by Tokyo University:
cancer
pancreas
advanced
peptide
vaccination
VEGFR1
 HLA
gemcitabine
IFA
Cancer of Pancreas
Neoplasms, Pancreas
Pancreas Cancer

Additional relevant MeSH terms:
Neoplasms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Endothelial Growth Factors
Antimetabolites, Antineoplastic
Antimetabolites
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Growth Substances

ClinicalTrials.gov processed this record on May 19, 2013