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

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: therapeutic autologous dendritic cells; Biological: trastuzumab; Drug: vinorelbine ditartrate

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 118 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Dendritic Cell Vaccine; 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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	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.	6 months following treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Response	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.	3 months following treatment

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI); Susan G. Komen Breast Cancer Foundation
• Investigators: Study Chair: Jonathan S. Serody, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• UNC Lineberger Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: August 4, 2004
• First Submitted That Met QC Criteria: August 4, 2004
• First Posted (Estimate): August 5, 2004

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: May 26, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Vinorelbine
• Other Study ID Numbers: LCCC 0310; P50CA058223 (U.S. NIH Grant/Contract); R21CA105837 (U.S. NIH Grant/Contract); KG100307 (Other Grant/Funding Number: Susan G Komen for the Cure)