Breast Cancer
Conditions
Keywords
stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, male breast cancer
Brief summary
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
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.
Interventions
BIOLOGICALHER-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.
OTHERflow cytometry
This is a laboratory test used to assess the antigen specific T cell population.
OTHERimmunohistochemistry staining method
This is a laboratory test used to identify CD3+, CD4+, CD45R0+, CD8+, and DC1a+ present in the skin biopsy.
PROCEDUREbiopsy
A 3mm punch biopsy is taken of the vaccine site. This is taken for laboratory analysis for immunohistochemical staining.
OTHERSterile 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.
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immunologic memory response to HER-2/neu (HER2) intracellular domain protein | 6 months after active immunization |
Secondary
| Measure | Time frame |
|---|---|
| Quantitate memory precursor frequency by intracellular cytokine staining | 3, 6, and 12 months after active immunization |
| Characterization of memory T-cell population by intracellular cytokine staining | 3, 6, and 12 months after active immunization |
Countries
United States
Outcome results
None listed