Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Women With Locally Recurrent or Metastatic Breast Cancer
| Status: | Completed |
|---|---|
| Conditions: | Breast Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 120 |
| Updated: | 4/21/2016 |
| Start Date: | January 2004 |
Phase II Trial Evaluating The Efficacy Of A Multiepitope Dendritic Cell Vaccine Given With Trastuzumab And Vinorelbine For The Treatment Of Women With Metastatic Breast Cancer That Express HLA-A0201
RATIONALE: Vaccines may make the body build an immune response to kill tumor cells.
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or
deliver tumor-killing substances to them without harming normal cells. Drugs used in
chemotherapy, such as vinorelbine, work in different ways to stop tumor cells from dividing
so they stop growing or die. Combining vaccine therapy with monoclonal antibody therapy and
chemotherapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving vaccine therapy together with
trastuzumab and vinorelbine works in treating women with locally recurrent or metastatic
breast cancer.
Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or
deliver tumor-killing substances to them without harming normal cells. Drugs used in
chemotherapy, such as vinorelbine, work in different ways to stop tumor cells from dividing
so they stop growing or die. Combining vaccine therapy with monoclonal antibody therapy and
chemotherapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving vaccine therapy together with
trastuzumab and vinorelbine works in treating women with locally recurrent or metastatic
breast cancer.
OBJECTIVES:
Primary
- Determine the efficacy of multiepitope autologous dendritic cell vaccine, trastuzumab
(Herceptin^®), and vinorelbine by measuring the change in the largest dimension of
metastatic lesions, in women with locally recurrent or metastatic breast cancer that
does not overexpress HER2/neu.
Secondary
- Determine the ability of this regimen to induce functional antigen-specific T cells in
these patients by measuring ex-vivo antigen-specific T-cell activity against
peptide-pulsed dendritic cells and tumor targets by tetramer staining and intracellular
cytokine assays.
OUTLINE:
- Autologous dendritic cell mobilization and harvest: All patients undergo autologous
dendritic cell mobilization with filgrastim (G-CSF) and/or sargramostim (GM-CSF)
subcutaneously daily for 4 days followed by apheresis. Mobilized peripheral blood is
processed for the production of dendritic cells by CD34-positive cell selection. The
dendritic cells are expanded and then pulsed with E75 and E90 peptides.
- Treatment: Patients receive vinorelbine IV over 6-10 minutes and trastuzumab (Herceptin
^®) IV over 90 minutes on day 1. Patients also receive autologous dendritic cells
pulsed with E75 and E90 peptides subcutaneously over 2-5 minutes on day 1*. Treatment
repeats every 14 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity.
NOTE: *If treatment is given locally, the vaccine therapy will be given at UNC-Chapel Hill
the following day.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study.
Primary
- Determine the efficacy of multiepitope autologous dendritic cell vaccine, trastuzumab
(Herceptin^®), and vinorelbine by measuring the change in the largest dimension of
metastatic lesions, in women with locally recurrent or metastatic breast cancer that
does not overexpress HER2/neu.
Secondary
- Determine the ability of this regimen to induce functional antigen-specific T cells in
these patients by measuring ex-vivo antigen-specific T-cell activity against
peptide-pulsed dendritic cells and tumor targets by tetramer staining and intracellular
cytokine assays.
OUTLINE:
- Autologous dendritic cell mobilization and harvest: All patients undergo autologous
dendritic cell mobilization with filgrastim (G-CSF) and/or sargramostim (GM-CSF)
subcutaneously daily for 4 days followed by apheresis. Mobilized peripheral blood is
processed for the production of dendritic cells by CD34-positive cell selection. The
dendritic cells are expanded and then pulsed with E75 and E90 peptides.
- Treatment: Patients receive vinorelbine IV over 6-10 minutes and trastuzumab (Herceptin
^®) IV over 90 minutes on day 1. Patients also receive autologous dendritic cells
pulsed with E75 and E90 peptides subcutaneously over 2-5 minutes on day 1*. Treatment
repeats every 14 days for up to 6 courses in the absence of disease progression or
unacceptable toxicity.
NOTE: *If treatment is given locally, the vaccine therapy will be given at UNC-Chapel Hill
the following day.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 17-37 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
- Histologically confirmed breast cancer
- Locally recurrent or metastatic disease
- HLA-A0201 positive by DNA genotyping
- HER2/neu expression at least 1+ by immunohistochemistry of tumor sample
- CNS metastases allowed provided on therapy for 3 months and stable
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 18 and over
Sex
- Female
Menopausal status
- Not specified
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- Hematocrit > 33%
Hepatic
- Transaminases ≤ 3 times upper limit of normal
- Bilirubin ≤ 2 times normal
- Hepatitis B surface antigen negative
Renal
- Creatinine < 2.0 mg/dL
Cardiovascular
- Ejection fraction > 45% by MUGA OR
- Left ventricular function normal by echocardiogram
- No serious cardiac condition that would preclude study participation or compliance
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No serious medical or psychiatric condition that would preclude study participation
or compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior biologic therapy allowed
Chemotherapy
- More than 30 days since prior cytotoxic chemotherapy
- No other concurrent chemotherapy
Endocrine therapy
- More than 30 days since prior hormonal therapy
- No concurrent hormonal therapy
- No concurrent systemic steroids
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- Concurrent bisphosphonates for bone metastases allowed
We found this trial at
1
site
101 Manning Drive
Chapel Hill, North Carolina 27514
Chapel Hill, North Carolina 27514
(919) 966-0000
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill One of the...
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