Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Women With Locally Recurrent or Metastatic Breast Cancer

Phase 2

Terminated

Conditions: Breast Cancer

Interventions: Biological: therapeutic autologous dendritic cells
Biological: trastuzumab
Drug: vinorelbine ditartrate

Registration Number: NCT00088985

Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 56

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dendritic Cell Vaccine	therapeutic autologous dendritic cells	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
Dendritic Cell Vaccine	trastuzumab	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
Dendritic Cell Vaccine	vinorelbine ditartrate	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

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	6 months following treatment	Response measured by Response Evaluation Criteria In Solid Tumors (RECIST), (Complete Response + Partial Response) Complete Response (CR)- Disappearance of all target lesions Partial Response (PR)-at least a 30% decrease in the longest diameters of target lesions, taking as reference the baseline longest diameter.

Secondary Outcome Measures

Name	Time	Method
Immune Response	3 months following treatment	Measured by intracellular cytokine staining for Interferon-gamma (INFgamma) and cluster of differentiation (CD107) up regulation and tetramer. A fourfold increase in the number of cluster of differentiation (CD8+) tetramers comparing prevaccine with peak postvaccine values indicated an immune response to the therapy.