Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective
      immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and
      trastuzumab, may increase the number of immune cells and make the immune response stronger.
      It is not yet known whether giving cyclophosphamide together with vaccine therapy is more
      effective with or without trastuzumab in treating patients with metastatic breast cancer.

      PURPOSE: This randomized phase II trial is studying the side effects of giving
      cyclophosphamide together with vaccine therapy and to see how well it works compared with
      giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients
      with metastatic breast cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To evaluate the safety of cyclophosphamide-modulated vaccination with vs without
           trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.

        -  To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs
           without trastuzumab in these patients.

        -  To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type
           hypersensitivity (DTH) and ELISPOT.

        -  To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.

      Secondary

        -  To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry of
           vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms,
           comparing cellular infiltrates to those seen in previous preclinical and clinical
           models.

        -  To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.

        -  To characterize the peripheral-memory T-cell pool.

      Tertiary

        -  To determine baseline and change in vaccine site-draining lymph node immunohistology and
           gene expression profile.

        -  To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T
           cells.

        -  To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated
           vaccination.

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

        -  Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic
           GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6
           weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
           Patients then receive a fourth vaccination at 6-8 months.

        -  Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV
           over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the
           absence of disease progression or unacceptable toxicity. Patients then receive a fourth
           vaccination at 6-8 months.

      Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of courses
      1 and 3 for biomarker analysis.

      After completion of study treatment, patients are followed periodically.
    

Intervention name(s): allogeneic GM-CSF-secreting breast cancer vaccine; trastuzumab; cyclophosphamide
Intervention type(s): Biological; Biological; Drug
Intervention description(s): Given intradermally; Given IV; Given IV
Intervention MeSH terms: Cyclophosphamide; Trastuzumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV breast cancer; male breast cancer