Clinical trial NCT00088985
Conditions: Breast Cancer
Keywords: recurrent breast cancer stage IIIB breast cancer stage IIIC breast cancer stage IV breast cancer
Sponsor: UNC Lineberger Comprehensive Cancer Center
Start date: 2004-01-01; Completion date: 2009-10-01
Enrollment: 56 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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 human epidermal growth factor receptor 2 (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 cluster of differentiation (CD)34-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 University of North Carolina (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.

Arms: arm 1: Dendritic Cells: Dosage: 20 x 106 dendritic cells (DCs) given per treatment Vinorelbine:25 mg/m2 will be administered i.v biweekly Trastuzumab: 6mg/Kg administered by i.v. biweekly
Interventions: intervention 1: therapeutic autologous dendritic cells intervention 2: trastuzumab intervention 3: vinorelbine ditartrate
Intervention descriptions: intervention 1: 10 μg/kg subcutaneously (sc) each day for four days or g-CSF at 5 μg/kg sc each day for four days with GM-CSF 250 μg/m2 sc each day for four days. G-CSF and/or GM- CSF will be self-administered. On the fifth day patients will have two intravenous lines placed in the apheresis area of the Blood Bank and then undergo a 15 litre apheresis collection intervention 2: 4 mg/kg intravenously, every 14 days intervention 3: Vinorelbine 25 mg/m2 will be administered intravenously, every 14 days

Protocol documents: