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

NCT00683085 | Terminated Phase 1 Results DMC

• 1 other identifier: IMSUT-PPKVEGFR10201
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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).

Conditions

Pancreatic Cancer; Pancreas Neoplasms

Keywords

cancer; pancreas; advanced; peptide; vaccination; VEGFR1; HLA; gemcitabine; IFA; Cancer of Pancreas; Neoplasms, Pancreas; Pancreas Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Number of Participants With Tumor Regression

  2 months

Study Arms (1)

Peptide vaccination

EXPERIMENTAL

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

Interventions

HLA-A*02:01-restricted VEGFR1-derived peptide vaccination BIOLOGICAL

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.

Also known as: VEGFR1-A2-770; TLFWLLLTL

Peptide vaccination

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tokyo University: lead
• Human Genome Center, Institute of Medical Science, University of Tokyo: collaborator

Study Sites (1)

Research Hospital, The Institute of Medical Science, The University of Tokyo

Minato-ku, Tokyo, 108-8639, Japan

Location

Related Publications (2)

• 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.

  PMID: 14512794 BACKGROUND

• 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.

  PMID: 17020992 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed

Results Point of Contact

• Title: Hitomi Nagayama, M.D., Ph.D. / Project Lecturer
• Organization: Research Hospital, The Institute of Medical Science, The University of Tokyo

zephyrus@ims.u-tokyo.ac.jp

+81-3-3443-8111

Study Officials

• Naohide Yamashita, MD, PhD

  Director, Research Hospital, Institute of Medical Science, Tokyo University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 16, 2008
• First Posted: May 23, 2008
• Study Start: May 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: July 22, 2011
• Results First Posted: December 17, 2010

Record last verified: 2011-07

Locations

JP (1)