Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2/Neu-Overexpressing Metastatic Breast Cancer

Summary

This is a feasibility study to examine combination therapy with Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine in patients with Stage IV HER-2/neu-overexpressing breast cancer. The main purposes of this study are to test the safety, clinical benefit, and bioactivity of vaccine therapy in combination with Cyclophosphamide and Trastuzumab in patients with HER-2/neu-overexpressing Stage IV breast cancer. This study will also to test whether the Cyclophosphamide can eliminate the suppressive influence of regulatory T cells, and whether Trastuzumab can increase antigen processing and presentation. These drug activities may make the immune system react better and enhance the effects of the vaccine in treating breast cancer. The vaccine consists of two irradiated allogeneic mammary carcinoma cell lines genetically modified to secrete human granulocyte-macrophage colony stimulating factor (GM-CSF). This open label, single arm study is designed to recruit up to 40 subjects to identify 20 research subjects with HER-2/neu-overexpressing Stage IV breast cancer eligible for study treatment.

Conditions

• Breast Neoplasms

Interventions

BIOLOGICAL

Allogeneic GM-CSF-secreting breast cancer vaccine

the vaccine containing a mixture of two GM-CSF-secreting allogeneic breast cancer cell lines (two parts 2T47D-V and one part 3SKBR3-7 mixed in a fixed dose of 5 X 108 cells for each patient and each vaccination cycle) on day 0.

DRUG

Trastuzumab

Trastuzumab is a humanized monoclonal antibody specific for the extracellular domain of HER-2/neu that is now one component of the standard of care for both early and late stage HER-2/neu-overexpressing breast cancers. It exerts a pleiotropic antitumor effect by multiple mechanisms. The antibody decreases heterodimer formation with other members of the epidermal growth factor receptor (EGFR) family, thereby indirectly inhibiting signaling through the Ras/Raf/mitogen-activated protein kinases (MAPK) and Phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt) pathways. It also inhibits tumor neovascularization, and augments apoptosis both in vitro and in vivo. Trastuzumab prevents cleavage of the extracellular domain of HER-2/neu, thus abrogating the constitutive activation of the remaining membrane-associated intracellular domain.

DRUG

Cyclophosphamide

The doses of Cyclophosphamide are based on previously reported clinical experience as well as our own preclinical data demonstrating augmented vaccine efficacy with CY-modulated vaccination. In particular, 300 mg/m2

Sponsors & Collaborators

• American Cancer Society, Inc.

  collaborator OTHER

• Avon Foundation

  collaborator OTHER

• Cancer Treatment Research Foundation

  collaborator OTHER

• The Commonwealth Fund

  collaborator OTHER

• United States Department of Defense

  collaborator FED

• Genentech, Inc.

  collaborator INDUSTRY

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  lead OTHER

Principal Investigators

• Leisha A Emens, M.D.,Ph.D. · Johns Hopkins University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-09-30

Primary Completion

2010-02-28

Completion

2010-02-28

Countries

• United States

Study Locations