Immune Response in Patients Who Have Undergone Vaccine Therapy for Stage III or Stage IV Breast Cancer That Overexpresses HER2

Study Overview
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Brief Summary
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RATIONALE: Studying the immune response to a vaccine made from HER2/neu protein may help doctors plan better treatment for patients with breast cancer that overexpresses HER2. PURPOSE: This clinical trial is studying the immune response in patients who have undergone vaccine therapy for stage III or stage IV breast cancer that overexpresses HER2.

Detailed Description
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OBJECTIVES: Primary Determine whether immunologic memory to the HER-2/neu (HER2) intracellular domain (ICD) protein has been generated by active immunization with a HER2 ICD plasmid-based vaccine by assessing the delayed-type hypersensitivity response to HER2 ICD peptides 6 months after vaccination in patients with HER2-overexpressing stage III or IV breast cancer. Secondary Characterize the memory T-cell population and quantitate memory precursor frequency at 3, 6, and 12 months after active immunization using intracellular cytokine staining. OUTLINE: This is an open-label study. Patients receive HER2 intracellular domain (ICD) protein mixture intradermally and sterile water injected intradermally (as a negative control) at 6 months post-vaccination with pNGVL3-hICD vaccine. Vital signs and injection site will be monitored prior to skin test and at 60 minutes post-test. Patients return 48-72 hours after skin test for delayed-type hypersensitivity (DTH) measurements. The injection site is biopsied and examined by immunohistochemistry for infiltrating T-cell and antigen-presenting cell populations. Blood is drawn at 3, 6, and 12 months post-vaccination for assessment of immune memory response. Blood draws are coordinated with parent study. Blood samples are examined by flow cytometry for the presence of memory markers including L-selectin, CD45 isoforms, cytokines, and CCR7. PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

Official Title
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Development of HER-2/Neu (HER2) ICD Memory Immunity After Vaccination With a Plasmid Encoding HER2 ICD in Patients With Advanced Stage HER2 Overexpressing Breast and Ovarian Cancers

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: HER-2/neu intracellular domain protein
* Other: flow cytometry
* Other: immunohistochemistry staining method
* Procedure: biopsy
* Other: Sterile water placement


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage III/IV breast cancer Completed chemotherapy Receiving trastuzumab (Herceptin®) monotherapy Successful completion of HER-2/neu (HER2) intracellular domain (ICD) plasmid-based vaccine trial (Protocol 01-9773-D06: A Phase I Safety and Efficacy Trial of a DNA Plasmid Based Vaccine Encoding the HER-2/neu Intracellular Domain In Subjects With HER-2/neu-Overexpressing Tumors) within the past 3 months Hormone receptor status not specified PATIENT CHARACTERISTICS: Male or female (male patients are not excluded) Menopausal status not specified Zubrod performance status 0 Unable to bear children (female patients) PRIOR CONCURRENT THERAPY: See Disease Characteristics No cytoreductive chemotherapy within the past 30 days No cytotoxic treatment and/or systemic corticosteroids within the past month Concurrent local radiotherapy or hormonal therapy allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: HER-2/neu intracellular domain protein|300mcg (100mcg/peptide) of the HER2 ICD peptide mixture per skin test. This will be injected intradermally on the back at 6 months post active immunization.|
|Other: flow cytometry|This is a laboratory test used to assess the antigen specific T cell population.|
|Other: immunohistochemistry staining method|This is a laboratory test used to identify CD3+, CD4+, CD45R0+, CD8+, and DC1a+ present in the skin biopsy.|
|Procedure: biopsy|A 3mm punch biopsy is taken of the vaccine site. This is taken for laboratory analysis for immunohistochemical staining.|
|Other: Sterile water placement|100mcg of sterile water will be administered intradermally on the back and serves as a negative control for the laboratory analysis. This will be injected intradermally on the back at 6 months post active immunization.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic memory response to HER-2/neu (HER2) intracellular domain protein |  | 6 months after active immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of memory T-cell population by intracellular cytokine staining |  | 3, 6, and 12 months after active immunization | 
| Quantitate memory precursor frequency by intracellular cytokine staining |  | 3, 6, and 12 months after active immunization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, male breast cancer