Phase 2 Study of Trastuzumab and Etoposide for Her2 Positive Breast Cancer
Condition: HER-2 Positive Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Etoposide; Trastuzumab
Intervention description: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles; intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Intervention MeSH terms: Trastuzumab; Etoposide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Her2 Positive; Breast Cancer; Metastatic

Summary:

      This study is for women and men who have previously treated metastatic (has spread to other
      parts in the body), Her2- positive breast cancer. The purpose of this study is to find out
      what effects (good and bad) the FDA-approved drugs etoposide and trastuzumab have on this
      type of breast cancer and to determine if these drugs are safe to use together. This research
      is being done to find more effective treatment for this type of condition.

      In this study, trastuzumab and etoposide will be given by intravenous infusion (IV; through a
      vein) on the first 3 days of every 3-week cycle. This is repeated for 6 cycles. After 6
      cycles, only trastuzumab will be given until worsening of disease. In this study, a small
      amount of your tissue that was collected when you had surgery will be evaluated in the lab to
      look at genetic differences among people and how those differences may affect a response to a
      specific drug or medicine. This testing will look for a gene called Top2A. Previous studies
      suggest that people who have both the Top2A and Her2 genes respond to certain chemotherapies
      (anti-cancer drugs) differently from those who only have the Her2 gene.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Females or males with histologic confirmation of breast carcinoma and diagnosis of
             metastatic breast adenocarcinoma

          -  Confirmed HER2 amplification by immunohistochemical staining (IHC) 3+ or FISH
             amplified (either primary or metastatic).

          -  Have had any number of prior HER2 targeted therapy containing chemotherapies for
             treatment of breast cancer

          -  Measurable extent of disease

          -  Life expectancy of 3 months or greater

          -  Patients must have adequate heart function, determined with ECHO or MUGA (ECHO
             preferred).

          -  Patients must have adequate bone marrow and organ function

          -  Patient of childbearing potential must be willing to use an effective means of
             contraception during their participation on trial

          -  Greater than 3 weeks from prior radiation or chemotherapy; more than 1 week from prior
             hormonal therapy; and more than 6 weeks from prior treatment with nitrosoureas or
             mitomycin.

          -  No serious intercurrent medical illness.

          -  Controlled metastatic CNS disease ≥ 3 months

          -  The ability to understand and willingness to sign a written informed consent form, and
             to comply with the protocol.

        Exclusion Criteria:

          -  Pregnant or nursing women

          -  Patients who are poor medical risk because of other non-malignant systemic disease or
             active, uncontrolled infection.

          -  Prior craniospinal radiation, or total body irradiation (TBI).

          -  Patients receiving G-CSF (filgrastim or pegfilgrastim) or thrombopoietin (or other
             platelet growth factors) within the 3 weeks prior to enrollment (erythropoietin is
             allowed).

          -  Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin).

          -  Prior radiation therapy within the last 3 weeks; prior radiation therapy to indicator
             lesion (unless objective disease recurrence or progression within the radiation portal
             has been documented since completion of radiation).

          -  Concomitant malignancies or previous malignancies within the last 5 years, with the
             exception of adequately treated basal or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix.

          -  Current symptoms of angina or uncontrolled arrhythmias, uncontrolled hypertension with
             systolic blood pressure >=170 or diastolic blood pressure >=110.

          -  Psychiatric illness precluding participation in study

          -  Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs,
             resulting in dyspnea at rest.

          -  Carcinomatous meningitis or CNS mets not controlled for ≥ 3 months.