Study of Avastin (Bevacizumab) to Reverse Acquired Estrogen Independence in Previously Hormone Responsive Metastatic Breast Ca.
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine if acquired hormone therapy resistance can be
      reversed by Avastin (Bevacizumab), as measured by time to disease progression and evaluate
      toxicity of the combination of hormone treatment plus Avastin (Bevacizumab).
    

Detailed description: 
      This is a single institution, open-label study designed to evaluate safety and efficacy of
      Avastin (Bevacizumab) combined with an endocrine agent in patients with estrogen and/or
      progesterone receptor positive metastatic breast carcinoma who have acquired resistance to at
      least one hormonal agent. Patients will be treated with the same hormonal agent that was used
      previously assuming that the patient had a partial or complete response (for at least 6
      months) followed by a clear disease progression using the Response Evaluation Criteria in
      solid Tumors (RECIST Criteria). Patients with stable disease for a prolonged time (for at
      least 6 months) will be also eligible to enter in the trial. Patients who have not had
      interval studies to evaluate disease response will be considered eligible if they have
      remained clinically stable (i.e. stable performance status (PS), no increasing pain) and on
      the same hormone for at least 6 months, and now they have signs and symptoms of clinical
      progression (i.e. elevated tumor markers, increasing bone pain, worsening performance
      status). Patients must have histologically confirmed measurable and/or evaluable metastatic
      breast cancer with positive estrogen and/or progesterone receptors. Patients can have up to
      an 8-12 week break in therapy (discontinuation of hormonal therapy) and still remain eligible
      for the study as long as the documentation of disease progression is determined before the
      8-12 week break in hormonal therapy.

      The type and dose of the hormonal agent that will be used in this trial will be the same one
      that the patient used before progression. Hormonal therapy may include any estrogen
      deprivation reagent such as Tamoxifen, Anastrazole, Exemestane, Letrozole, or Fulvestrant.
      All patients will receive Avastin (Bevacizumab) 15 mg/kg IV every three weeks. Based on
      statistical evaluations, 30 patients will be enrolled. The first evaluation of efficacy will
      be done at week 6; patients with objective response or stable disease will continue therapy
      with re-staging every 6 weeks until evidence of disease progression. Patients with
      progression of disease will be taken off study (see appendix A). PET scan will be done at
      baseline and only in the first evaluation (6 weeks) to obtain early "metabolic response data"
      that will be correlated with objective response and time to disease progression (PET data on
      week 6 will not be used to evaluate response and to make therapeutic decisions). PET
      "metabolic response" will be defined as a >20% reduction in Standardized Uptake Value (SUV).
      Safety will be assessed by the recording of adverse events, serious adverse events,
      laboratory test results, and changes in vital signs. A positive response to Avastin
      (Bevacizumab) (reversal of hormonal resistance) will be defined as an objective response or
      stable disease of ≥ 3 months duration. All concomitant medication must be documented.
      Additionally, any diagnostic, therapeutic or surgical procedure performed during the study
      period, should be recorded including the date, indication, description of the procedure(s)
      and any clinical findings.
    

Intervention name(s): Avastin; Hormonal therapy
Intervention type(s): Drug; Drug
Intervention description(s): All patients will received Avastin 15 mg/kg IV every three weeks. The first evaluation will be done at Week 6. Patients with objective response or stable disease will continue therapy with restaging every 6 weeks until evidence of disease progression. Patients with progression of disease will be taken off study.; aromatase inhibitor (letrozole 2.5mg/d PO, anastrazole 1mg/d PO, or exemestane 25mg/d PO)or Selective Estrogen Receptor Modulator (SERM) (tamoxifen 20mg/d PO)
Other intervention name(s): Bevacizumab; Femara (letrozole); Arimidex (anastrazole); Aromasin (exemestane); Nolvadex (tamoxifen)
Intervention MeSH terms: Tamoxifen; Bevacizumab; Letrozole; Exemestane
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Breast cancer; Metastatic breast cancer; Hormonal therapy; Bevacizumab