Fulvestrant and/or Trastuzumab as First-Line Therapy in Treating Postmenopausal Women With Stage IV Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Faslodex; Herceptin
Intervention description: Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter.; Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly
Intervention MeSH terms: Trastuzumab; Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using
      fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes.
      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. It is not yet known whether giving
      fulvestrant together with trastuzumab is more effective than giving fulvestrant or
      trastuzumab alone in treating breast cancer.

      PURPOSE: This randomized phase II trial is studying how well fulvestrant and/or trastuzumab
      works as first-line therapy in treating postmenopausal women with stage IV breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female patient, postmenopausal, defined as a woman fulfilling any one of the following
             criteria:

               -  Age 60 years or older

               -  Age 45 years or older with amenorrhea for > 12 months with an intact uterus

               -  Follicle-stimulating hormone and estradiol levels within post-menopausal range

               -  Having undergone a bilateral oophorectomy

          -  Histologically or cytologically proven adenocarcinoma of the breast

          -  Subjects must have archived rumor tissue available to compare the clinical response
             with tumor expression of biomarkers, such as HER-2, ER and PR; archived tissue will be
             used to confirm HER-2, ER and PR status, but results will not be used to determine
             subject eligibility for the study

          -  HER2-positive disease

          -  ER-positive and/or PR-positive disease

          -  ECOG performance status 0-2

          -  Life expectancy > 24 weeks

          -  Left ventricular ejection fraction > lower limit of normal

          -  No prior chemotherapy, endocrine therapy, Herceptin, or other biologic or
             investigational therapy for metastatic breast cancer

          -  No more than two prior endocrine agents in the adjuvant setting as single- or
             sequential-therapy is permitted, but no prior Faslodex therapy is permitted. A 1-month
             treatment-free period is required prior to receiving the first dose of trial
             treatments

          -  Prior adjuvant chemotherapy is permitted

          -  Prior adjuvant Herceptin permitted

          -  At least 1 month since prior surgery, radiotherapy, or endocrine therapy, with
             complete recovery from the effects of these interventions

          -  Patients must have ended any hormone replacement therapy at least 1 month prior to
             receiving the first dose of trial therapy

          -  Patients treated with bisphosphonates may enroll, with heir bone lesions only
             assessable for disease progression

          -  Patient is accessible and willing to comply with treatment and follow-up

          -  Patient is willing to provide written informed consent prior to the performance of any
             study-related procedures

          -  Required laboratory values:

               -  Absolute neutrophil count > 1.5 x 10^9/L

               -  Hemoglobin > 10g/dL

               -  Platelet count > 100 x 10^9/L

               -  Creatinine < 2.0 mg/dL

               -  Total bilirubin < 1.5 x upper limit of normal

               -  AST and ALT < 2.5 x ULN

        Exclusion Criteria:

          -  Prior chemotherapy, hormonal therapy, Herceptin or other investigational therapy for
             metastatic breast cancer

          -  Prior treatment with Faslodex

          -  Concurrent therapy with any other non-protocol anti-cancer therapy

          -  Current or prior history of brain metastases

          -  History of any other malignancy within the past 5 years, with the exception of
             non-melanoma skin cancer or carcinoma-in-situ of the cervix

          -  Clinically significant cardiovascular disease, New York Heart Association Class II or
             greater congestive heart failure, or serious cardiac arrhythmia requiring medication

          -  Prior exposure of > 360 mg/m2 doxorubicin or liposomal doxorubicin, > 120 mg/m2
             mitoxantrone, > 90 mg/m2 idarubicin, or > 720 mg/m2 epirubicin

          -  Active, uncontrolled infection requiring parenteral antimicrobials

          -  The presence of any other medical or psychiatric disorder that, in the opinion of the
             treating physician, would contraindicate the use of the drugs in this protocol or
             place the subject at undue risk for treatment complications

          -  Inability to comply with the study protocol or follow-up procedures

          -  Known hypersensitivity to any of the drugs used in this protocol or to active or
             inactive excipients of Faslodex

          -  History of bleeding diasthesis

          -  Long-term anticoagulant therapy other than anti-platelet therapy, such as with
             warfarin