Clinical trial NCT00088985: Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Women With Locally Recurrent or Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: recurrent breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Susan G. Komen Breast Cancer Foundation
First posted: 2004-08-05
Enrollment: 56
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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
* Central Nervous System (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

* Eastern Cooperative Oncology Group (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 multigated acquisition scan (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

Primary outcomes:
measure: Overall Response Rate
timeFrame: 6 months following treatment
Secondary outcomes:
measure: Immune Response
timeFrame: 3 months following treatment
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Jonathan S. Serody, MD
role: STUDY_CHAIR
References: