Trastuzumab, Cyclophosphamide, and Vaccine Therapy in Treating Patients With High-Risk or Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: allogeneic GM-CSF-secreting breast cancer vaccine; trastuzumab; cyclophosphamide; flow cytometry; immunoenzyme technique; immunohistochemistry staining method; laboratory biomarker analysis; pharmacological study; biopsy
Intervention description: Day 0 : Allogeneic GM-CSF-secreting Breast Cancer Vaccine administered as:
12 intradermal injections of a divided total dose of 5 x108 cells.; 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; Cyclophosphamide 200mg/m2 IV in NS 100ml over 30 minutes on Day -1 ONLY. Note: there are no dose modifications for Cyclophosphamide.; Samples will be analyzed by flow cytometry using Cell Quest software; Measuring Immune Priming In Vivo By Vaccine Site Biopsies; skin biopsy to be performed on day 3 and day 7 for cycle 1 and 3 only
Intervention MeSH terms: Cyclophosphamide; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: 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

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.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  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

        PATIENT CHARACTERISTICS:

          -  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

        PRIOR CONCURRENT THERAPY:

          -  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