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

Breast Cancer Clinical Trial

— NRR  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00088985
• Other study ID #: LCCC 0310
• Secondary ID: UNC-GCRC-2102-OR
• Status: Terminated
• Phase: Phase 2
• First received: August 4, 2004
• Last updated: February 10, 2017
• Start date: January 2004
• Est. completion date: October 2009

Study information

• Verified date: February 2017
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 55
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• therapeutic autologous dendritic cells
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
• trastuzumab
4 mg/kg intravenously, every 14 days

Drug:
• vinorelbine ditartrate
Vinorelbine 25 mg/m2 will be administered intravenously, every 14 days

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate	Response measured by RECIST criteria	6 months following treatment
Secondary	Immune response	measured by ELISPOT tetramer	3 months following treatment