Histocompatibility Leukocyte Antigen (HLA)-A*0201 Restricted Peptide Vaccine Therapy in Patients With Breast Cancer

Phase I/II Study of Multiple-Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*0201 in Treating Patients With Refractory Breast Cancer

The purpose of this study is to evaluate the safety and time to progression of HLA-A*0201 restricted epitope peptides VEGFR1 and VEGFR2 emulsified with Montanide ISA 51 in advanced breast cancer patients.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: VEGFR1 and VEGFR2

Detailed Description

VEGF receptor 1 and 2 are essential targets to tumor angiogenesis, and we identified that peptides derived from these receptors significantly induce the effective tumor specific CTL response in vitro and vivo. According to these findings, in this trial, we evaluate the safety, immunological and clinical response of those peptides. Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection. Repeated cycles of the vaccine will be administered until patients develop progressive disease or unacceptable toxicity, whichever occurs first. In the phase I study, we evaluate the safety and tolerability of these peptide vaccine. In the following phase II study, we evaluate the immunological and clinical response of this vaccine therapy.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Minato-ku, Tokyo, Japan, 108-8639
      • The Institute of Medical Science, The University of Tokyo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Advanced or recurrent breast cancer
• Resistant against anthracycline-based and taxane-based chemotherapy or difficult to continue the chemotherapy due to intolerable side effect(s)
• Resistant against trastuzumab or difficult to continue it due to intolerable side effect(s) when her-2 is positive
• ECOG performance status 0-2
• Life expectancy > 3 months
• HLA-A*0201

• Laboratory values as follows

  • 2000/mm3<WBC<15000/mm3
  • Platelet count>100000/mm3
  • Bilirubin < 3.0mg/dl
  • Asparate transaminase < 150IU/L
  • Alanine transaminase < 150IU/L
  • Creatinine < 3.0mg/dl
• Able and willing to give valid written informed consent

Exclusion Criteria:

• Pregnancy(woman of childbearing potential:Refusal or inability to use effective means of contraception)
• Breastfeeding
• Active or uncontrolled infection
• Unhealed external wound
• Concurrent treatment with steroids or immunosuppressing agent
• Prior chemotherapy,radiation therapy, or immunotherapy within 4 weeks
• Uncontrolled brain and/or intraspinal lesion(s)
• Decision of unsuitableness by principal investigator or physician-in-charge

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Peptide administered	Biological: VEGFR1 and VEGFR2; Patients will be vaccinated twice a week for 8 weeks. On each vaccination day, VEGFR1 peptide (1mg) and VEGFR2 peptide (1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
safety(Phase I:toxicities as assessed by NCI CTCAE version3) and efficacy(Phase II:Feasibility as evaluated by RECIST)	2 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate immunological responses	2 months

Collaborators and Investigators

• Sponsor: Tokyo University
• Collaborators: Human Genome Center, Institute of Medical Science, University of Tokyo

Publications and helpful links

General Publications

• Li Y, Wang MN, Li H, King KD, Bassi R, Sun H, Santiago A, Hooper AT, Bohlen P, Hicklin DJ. Active immunization against the vascular endothelial growth factor receptor flk1 inhibits tumor angiogenesis and metastasis. J Exp Med. 2002 Jun 17;195(12):1575-84. doi: 10.1084/jem.20020072. Erratum In: J Exp Med 2002 Aug 19;196(4):557.
• 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.
• Wada S, Tsunoda T, Baba T, Primus FJ, Kuwano H, Shibuya M, Tahara H. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res. 2005 Jun 1;65(11):4939-46. doi: 10.1158/0008-5472.CAN-04-3759.

Helpful Links

• Research Hospital, the Institute of Medical Science, the University of Tokyo

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Anticipated): April 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: May 12, 2008
• First Submitted That Met QC Criteria: May 12, 2008
• First Posted (Estimate): May 14, 2008

Study Record Updates

• Last Update Posted (Estimate): December 29, 2009
• Last Update Submitted That Met QC Criteria: December 28, 2009
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: Peptide Vaccine; HLA-A*0201; VEGFR1; VEGFR2
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Breast-A02-I, II