Vaccine Therapy With or Without Cyclophosphamide and Doxorubicin in Women With Stage IV Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Vaccines made from a person's tumor cells may make the body build an immune
      response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide and
      doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or
      die. Combining vaccine therapy with cyclophosphamide and doxorubicin may kill more tumor
      cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of cyclophosphamide
      and doxorubicin when given with vaccine therapy in treating women with stage IV breast
      cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety of vaccination comprising allogeneic sargramostim
           (GM-CSF)-secreting breast cancer cells with or without immunomodulation using
           cyclophosphamide and doxorubicin in women with stage IV breast cancer.

        -  Determine the doses of cyclophosphamide and doxorubicin that maximize vaccine-induced
           immunity, in terms of immune response to HER2/neu, in patients treated with these
           regimens.

        -  Compare in vivo immune response induced by these regimens, as measured by
           immunohistochemical analysis of vaccine site biopsies from these patients, with
           responses seen in prior preclinical and clinical studies.

      Secondary

        -  Determine the time to disease progression in patients treated with these regimens.

      OUTLINE: This is a dose-finding study.

      The first 6 patients receive 1 of 2 doses of vaccine comprising allogeneic sargramostim
      (GM-CSF)-secreting breast cancer cells intradermally (ID) on day 0. Subsequent patients
      receive cyclophosphamide IV on day -1, vaccine at the higher dose ID on day 0, and
      doxorubicin IV on day 7. Treatment in all patients repeats every 4-6 weeks for 3 courses in
      the absence of disease progression or unacceptable toxicity. Patients with stable or
      responding disease after the third course receive a fourth course of treatment at
      approximately 4 months after completion of the third course.

      Cohorts of 2-3 patients receive a fixed dose of vaccine in combination with escalating doses
      of doxorubicin and cyclophosphamide. Doses of cyclophosphamide and doxorubicin are escalated
      until an optimal dose of combination chemotherapy with a fixed dose of vaccine is achieved.

      Patients are followed at 1 month and 4 months after completion of study therapy and then
      annually thereafter.

      PROJECTED ACCRUAL: A total of 6-60 patients will be accrued for this study.
    

Intervention name(s): allogeneic GM-CSF-secreting breast cancer vaccine; cyclophosphamide; doxorubicin hydrochloride
Intervention type(s): Biological; Drug; Drug
Intervention description(s): The first three patients will receive a dose of 5 X 107 cells, and the next three will receive a dose of 5 X 108 cells. Then, if these two doses of vaccine alone are found to be safe, a fixed vaccine dose of 5 X 108 cells will be tested in combination with chemotherapy based on the safety of the allogeneic breast vaccine alone and the safety and bioactivity of a dose of 5 X 108 cells in the allogeneic pancreatic vaccine trial; This trial will be a dose ranging study of a fixed sequence of drug doses in a three by three factorial matrix modeled after the theories of Plackett and Burman (Plackett et al., 1946), and is designed to determine the doses of CY and DOX that maximize the immunologic response to vaccination; This trial will be a dose ranging study of a fixed sequence of drug doses in a three by three factorial matrix modeled after the theories of Plackett and Burman (Plackett et al., 1946), and is designed to determine the doses of CY and DOX that maximize the immunologic response to vaccination
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IV breast cancer; recurrent breast cancer