Vaccine Therapy, Trastuzumab, and Vinorelbine in Treating Patients With Locally Recurrent or Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: sargramostim; therapeutic autologous dendritic cells; trastuzumab; vinorelbine ditartrate
Intervention description: All patients will receive Leukine (GM-CSF) at 250 mcg/m2 starting one day after the administration of chemotherapy x 7 days. Patients with neutrophil counts below 1,000/mm3 on day 8 will continue GM-CSF therapy until the neutrophil count is greater than 1,000/mm3.; patients will receive (10 x 106) peptide-pulsed DCs given by i.d injection into either axilla or the inguinal region with each peptide given into a separate site. The total dose will be 20 x 106 DCs given per treatment.; Trastuzumab will be infused in the side-port of a freely flowing IV over 90 minutes and at 6mg/kg if the subject has not previously received Trastuzumab, or if it has been more than 30 days since any prior trastuzumab administration. If the subject has previously received Trastuzumab within 30 days and has no adverse history with the drug, the infusion will be given over 30 minutes. If the subject is currently receiving Trastuzumab, the first study infusion will be given at 4mg/kg over 30 minutes. Subsequently, Trastuzumab will be infused at 4 mg/kg in the side-port of a freely flowing IV over 30 minutes.; Vinorelbine 25 mg/m2 will be administered IV over six to ten minutes into the side port of a freely flowing IV line.
Intervention MeSH terms: Trastuzumab; Vinorelbine; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Vaccines made from a person's white blood cells may help the body build an
      effective immune response to kill tumor cells. 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 vinorelbine, work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Giving vaccine
      therapy together with trastuzumab and vinorelbine may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving vaccine therapy together with
      trastuzumab and vinorelbine works in treating patients with locally recurrent or metastatic
      breast cancer.
    

Eligibility criteria:

        PATIENT ELIGIBILITY

        4.1 Inclusion Criteria 4.1.1 Histologically proven metastatic breast cancer with measurable
        or evaluable disease per investigator discretion.

        4.1.2 Patients must be 18 years of age or older. Women of child bearing potential must be
        practicing barrier or oral contraception for the duration of the study, or documented as
        surgically sterile or one year post-menopausal.

        4.1.3 Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (See Appendix A).

        4.1.5 Cardiac function by multigated acquisition scan (MUGA) with an ejection fraction (EF)
        > 45% or an echocardiogram that shows normal left ventricle (LV) function.

        4.1.6 Serum Creatinine < 2.0 mg/dl. 4.1.7 Hepatic transaminases (alanine aminotransferase
        (ALT) and aspartate aminotransferase (AST)) ≤3.0 times the upper limit of normal if no
        liver metastases or ≤5 times the upper limit of normal if liver metastases are present.

        4.1.8 Bilirubin no more than 2 times normal.

        4.1.9 Seronegative for HIV.

        4.1.10 Negative for Hepatitis B surface antigen.

        4.1.11 Signed and dated informed consent.

        4.1.12 HLA A0201+ by DNA genotyping.

        4.1.13 Absolute neutrophil count greater than 1,500/mm3. Platelet count greater 100,000/mm3
        and hemoglobin greater than or equal to 10

        4.1.14. 3+ expression of HER-2/neu from original pathology (diagnostic) tumor sample by
        Immunohistochemistry (IHC) or 2+ expression by IHC with gene amplification by fluorescence
        in situ hybridization (FISH).

        4.1.15. Patients will be eligible even if they have failed treatment for metastatic breast
        cancer with trastuzumab and a chemotherapy agent other than vinorelbine or if they have
        progressed within 12 months of receiving adjuvant chemotherapy using trastuzumab and a
        taxane.

        4.2 Exclusion Criteria

        4.2.1 Patients with any serious medical, cardiac, or psychiatric condition which, in the
        opinion of the investigator, would make the patient unsuitable for study participation or
        would impede probable compliance with the protocol.

        4.2.2 Patients with central nervous system metastases must have stable disease for at least
        3 months prior to study entry.

        4.2.3 Patient is currently taking steroid medications. Systemic steroid treatment is not
        allowed.

        4.2.4 Patients that have failed prior therapy with vinorelbine + trastuzumab will not be
        eligible for therapy.

        4.2.5 Patient has received hormonal or cytotoxic chemotherapy within 14 days of apheresis
        and within 28-30 days prior to study treatment.