Trastuzumab, Cyclophosphamide, and Vaccine Therapy in Treating Patients With High-Risk or Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00847171
Recruitment Status : Unknown
Verified May 2013 by Sidney Kimmel Comprehensive Cancer Center.
Recruitment status was:  Active, not recruiting
First Posted : February 19, 2009
Last Update Posted : May 29, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center

Brief Summary:

RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. Giving trastuzumab together with cyclophosphamide and vaccine therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects of giving trastuzumab together with cyclophosphamide and vaccine therapy in treating patients with high-risk or metastatic breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: allogeneic GM-CSF-secreting breast cancer vaccine Biological: trastuzumab Drug: cyclophosphamide Other: flow cytometry Other: immunoenzyme technique Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy Phase 2

Detailed Description:



  • To evaluate the safety of allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine in combination with trastuzumab (Herceptin®) and cyclophosphamide in patients with high-risk or metastatic HER2/neu-overexpressing breast cancer.
  • To measure the HER2/neu-specific CD4+ T-cell response by delayed-type hypersensitivity.
  • To measure the magnitude of HER2/neu-specific CD8+ T-cell responses by ELISPOT.


  • To assess the impact of trastuzumab on immune priming in vivo by IHC.
  • To measure the impact of cyclophosphamide pretreatment on CD4+CD25+ regulatory T cells by flow cytometry.
  • To determine the time to disease progression.


  • To develop the tandem tetramer/CD107a cytotoxicity assay for HER2/neu-specific CD8+ T cells.
  • To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination.

OUTLINE: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day -1 of the first course of vaccination and continuing until the completion of the last course of vaccination. Patients also receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine intradermally on day 0. Treatment with cyclophosphamide and the vaccine repeats every 27-42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth course of cyclophosphamide and vaccine approximately 6-8 months after the first course.

Patients undergo delayed-type hypersensitivity testing and blood sample collection at baseline and periodically during study for immunologic laboratory studies. Blood samples are analyzed for serum GM-CSF levels by pharmacokinetic studies and for immune monitoring by ELISPOT and flow cytometry. Skin punch biopsies are also performed periodically and analyzed by IHC.

After completion of study treatment, patients are followed periodically.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Bioactivity Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-Secreting Breast Tumor Vaccine for the Treatment of Patients With High Risk/ Metastatic HER-2/Neu- Overexpressing Breast Cancer With No Evidence of Disease
Study Start Date : December 2008
Estimated Primary Completion Date : June 2013
Estimated Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Intervention Details:
    Biological: allogeneic GM-CSF-secreting breast cancer vaccine

    Day 0 : Allogeneic GM-CSF-secreting Breast Cancer Vaccine administered as:

    12 intradermal injections of a divided total dose of 5 x108 cells.

    Biological: trastuzumab

    Patient HAS received prior Trastuzumab within the last two weeks, give Trastuzumab 2 mg/kg weekly on Day -1 for 5 weeks.

    Patient has NOT received Trastuzumab within the last two weeks, give On Cycle 1, Day -1 ONLY, Loading dose 4 mg/kg

    Other Name: Herceptin
    Drug: cyclophosphamide
    Cyclophosphamide 200mg/m2 IV in NS 100ml over 30 minutes on Day -1 ONLY. Note: there are no dose modifications for Cyclophosphamide.
    Other Name: Cytoxan
    Other: flow cytometry
    Samples will be analyzed by flow cytometry using Cell Quest software
    Other: immunoenzyme technique Other: immunohistochemistry staining method
    Measuring Immune Priming In Vivo By Vaccine Site Biopsies
    Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy
    skin biopsy to be performed on day 3 and day 7 for cycle 1 and 3 only

Primary Outcome Measures :
  1. Safety (local and systemic toxicity) as assessed by NCI CTCAE v3.0 [ Time Frame: 4 years ]
  2. Immunologic response (HER2/neu-specific immune response and delayed-type hypersensitivity response to HER2/neu-derived peptides) [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Clinical benefit as assessed by rate of progression-free survival [ Time Frame: 4 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed adenocarcinoma of the breast, meeting one of the following criteria:

    • Metastatic disease
    • High-risk disease, defined as early-stage disease with pathologic involvement of locoregional lymph nodes

      • Patients who are/will be receiving standard adjuvant trastuzumab [Herceptin®] for high-risk disease will participate in this study during the single-agent trastuzumab portion of their therapy
  • No clinical or radiographical evidence of active disease
  • Not eligible for therapy of known curative potential for metastatic breast cancer
  • HER2/neu-overexpressing disease, defined as HER2/neu positive by IHC 3+ staining or by FISH+ amplification
  • Stable CNS disease allowed provided it has been adequately treated and is not under active treatment
  • Hormone receptor status not specified


  • Menopausal status not specified
  • ECOG performance status 0-1
  • ANC > 1,000/mm^3
  • Platelet count > 100,000/mm^3
  • Serum creatinine < 2.0 mg/dL
  • Serum bilirubin ≤ 2.0 mg/dL (unless elevation is due to known Gilbert's syndrome)
  • AST/ALT ≤ 2 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Cardiac ejection fraction normal by MUGA OR ≥ 45% by ECHO
  • No other malignancies within the past 5 years, except for carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, or superficial bladder cancer
  • No prior or currently active autoimmune disease* requiring management with systemic immunosuppression, including any of the following:

    • Inflammatory bowel disease
    • Systemic vasculitis
    • Scleroderma
    • Psoriasis
    • Multiple sclerosis
    • Hemolytic anemia or immune-mediated thrombocytopenia
    • Rheumatoid arthritis
    • Systemic lupus erythematosus
    • Sjögren syndrome
    • Sarcoidosis
    • Other rheumatologic disease
  • No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
  • HIV-negative
  • No evidence of active acute or chronic infection
  • No uncontrolled medical problems
  • No active major medical or psychosocial problems that could be complicated by study participation
  • No corn allergy
  • No known severe hypersensitivity to trastuzumab (except for mild to moderate infusion reactions that are easily managed and do not recur) NOTE: *Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed


  • Any number of prior chemotherapy regimens for metastatic breast cancer allowed
  • Prior or concurrent trastuzumab in the adjuvant or metastatic setting allowed
  • More than 28 days since prior and no concurrent systemic oral steroids

    • Topical, ocular, or nasal steroids allowed
  • More than 28 days since prior and no concurrent chemotherapy, radiotherapy, or biologic therapy (except trastuzumab)
  • More than 28 days since prior and no concurrent participation in another investigational clinical trial involving a new drug
  • Concurrent endocrine therapy or bisphosphonates allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00847171

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Leisha A. Emens, MD, PhD Sidney Kimmel Comprehensive Cancer Center

Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT00847171     History of Changes
Other Study ID Numbers: J0885 CDR0000634155
P30CA006973 ( U.S. NIH Grant/Contract )
First Posted: February 19, 2009    Key Record Dates
Last Update Posted: May 29, 2013
Last Verified: May 2013

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
male breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
HER2-positive breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists