Study of Avastin (Bevacizumab) to Reverse Acquired Estrogen Independence in Previously Hormone Responsive Metastatic Breast Ca.
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Avastin; Hormonal therapy
Intervention description: 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)
Intervention MeSH terms: Tamoxifen; Bevacizumab; Letrozole; Exemestane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: Female
Minimum age: 19 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Breast cancer; Metastatic breast cancer; Hormonal therapy; Bevacizumab

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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have cytologically or histologically proven breast cancer which is
             estrogen receptor or progesterone receptor positive and is locally advanced and /or
             metastatic.

          -  Give written informed consent prior to study specific screening procedures, with the
             understanding that the patient has the right to withdraw from the study at any time,
             without prejudice (Appendix E).

          -  Be female and greater than or equal to 19 years of age (age limit required by the
             State of Alabama). Women of childbearing potential must have a negative pregnancy test
             and must be willing to consent to using effective contraception while on treatment and
             for a reasonable period thereafter. Should a woman become pregnant or suspect she is
             pregnant while participating in this study, she should inform her treating physician
             immediately.

          -  Be ambulatory (outpatient) and have an Eastern Cooperative Oncology Group (ECOG) PS <2
             (Appendix B).

          -  Previous treatment: Patients must have responded to first or second line hormonal
             therapy (Partial and complete response greater than 6 months using RECIST criteria.
             Patients with stable disease for more than 6 months will be eligible) and became
             resistant to the hormonal agent. They must remain on the current hormone therapy to
             which they initially responded but now are resistant.

          -  Clear documentation of acquired hormonal resistance.

          -  Evaluable disease will be considered eligible, but measurable disease according to
             RECIST criteria will be preferable (Appendix C). The target lesion(s) must not have
             been previously irradiated (newly arising lesions in previously irradiated areas are
             acceptable).

          -  Patients must have adequate organ and marrow function as defined as follows: absolute
             neutrophil count > 1,500/mm3, hemoglobin > 8.0 g/dl, platelets > 75,000/mm3, total
             bilirubin < 2 mg/dl, serum creatinine < 2 mg/dl, transaminases (AST, ALT) may be up to
             2.5 x institutional upper limit of normal for patients with no liver metastases and up
             to 5 x institutional upper normal limit for patients with documented liver metastases.
             In addition < 1 gr of protein in 24 hr urine collection and urine protein/creatinine
             ratio < 1.0

          -  Prior chemotherapy does not exclude patients from study as long as the current therapy
             was hormonal therapy alone.

          -  Patients with de novo hormone therapy resistance will not be eligible.

          -  No life threatening parenchymal disease or rapidly progressing disease warranting
             cytotoxic chemotherapy.

          -  No history of brain metastases.

          -  No history of thrombosis during the previous year, including transient ischemic
             attack.

          -  Hypertension must be controlled (< 150/100 mmHg).

          -  Ejection Fraction > 50%.

        Exclusion Criteria:

          -  Patients who are "de novo" resistant to hormone therapy.

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study other than this Genentech-sponsored
             bevacizumab cancer study.

          -  Blood pressure of >150/100 mmHg

          -  Unstable angina

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infarction within 6 months

          -  History of stroke within 6 months

          -  Clinically significant peripheral vascular disease

          -  History of a bleeding disorder

          -  Presence of central nervous system or brain metastases

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0, anticipation of need for major surgical procedure during the course of
             the study

          -  Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to Day 0

          -  Pregnant (positive pregnancy test) or lactating

          -  Urine protein: creatinine ratio greater than or equal to 1.0 at screening. Patients
             demonstrating > 1 gr of protein in 24 hr urine collection within 4 weeks prior to
             study entry will not participate in the trial.

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Day 0

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Unwilling or unable to comply with the protocol for the duration of the study.

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Previously radiated area(s) must not be the only site of disease.

          -  History of another malignancy within the last five years except cured basal cell
             carcinoma of skin and carcinoma in-situ of uterine cervix.