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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00088985
First received: August 4, 2004
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Biological: therapeutic autologous dendritic cells
Biological: trastuzumab
Drug: vinorelbine ditartrate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Response rate [ Time Frame: 6 months following treatment ] [ Designated as safety issue: No ]
    Response measured by RECIST criteria


Secondary Outcome Measures:
  • Immune response [ Time Frame: 3 months following treatment ] [ Designated as safety issue: No ]
    measured by ELISPOT tetramer


Enrollment: 55
Study Start Date: January 2004
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dendritic Cell Vaccine
Dendritic Cells: Dosage: 20 x 106 DCs given per treatment Vinorelbine:25 mg/m2 will be administered i.v biweekly Trastuzumab: 6mg/Kg administered by i.v. biweekly
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
Biological: trastuzumab
4 mg/kg intravenously, every 14 days
Drug: vinorelbine ditartrate
Vinorelbine 25 mg/m2 will be administered intravenously, every 14 days

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00088985

Locations
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Investigators
Study Chair: Jonathan S. Serody, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00088985     History of Changes
Other Study ID Numbers: LCCC 0310, UNC-GCRC-2102-ORC, CDR0000377732
Study First Received: August 4, 2004
Last Updated: February 15, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
recurrent breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vinorelbine
Vinblastine
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014