Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases
Condition: Metastatic Breast Cancer; Breast Cancer; Progressive Breast Cancer
MeSH terms: Breast Neoplasms; Brain Neoplasms
Intervention: carboplatin; bevacizumab; herceptin
Intervention MeSH terms: Bevacizumab; Trastuzumab; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: carboplatin; bevacizumab

Summary:

      The purpose of this research study is to determine how well the combination of bevacizumab
      and carboplatin works in treating breast cancer that has spread to the brain. Bevacizumab is
      an antibody (a protein that attacks a foreign substance in the body) that is made in the
      laboratory. Bevacizumab works differently from the way chemotherapy drugs work. Usually
      chemotherapy drugs attack fast growing cancer cells in the body. Bevacizumab works to slow or
      stop the growth of cells in cancer tumors by decreasing the blood supply to the tumors. When
      the blood supply is decreased, the tumors don't get the oxygen and nutrients they need to
      grow. Carboplatin is in a class of drugs known as platinum-containing compounds and has been
      approved for use in the treatment of ovarian cancer. Information from other research studies
      suggests that the combination of bevacizumab with carboplatin may be effective in treating
      breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed invasive breast cancer, with metastatic
             disease. patients without pathologic or cytologic confirmation of metastatic disease
             should have unequivocal evidence of metastasis by physical exam or radiologic study

          -  Measurable disease. Patients must have measurable CNS disease, defined as at least one
             parenchymal brain lesion that can be accurately measured in at least one dimension
             with longest dimension >/= 10mm by local radiology review

          -  New or progressive CNS lesions, as assessed by the patient's treating physician

          -  No increase in corticosteroid dose in the week prior to the baseline brain MRI

          -  18 years of age or older

          -  Life expectancy of greater than 12 weeks

          -  Eastern Cooperative Oncology Group Performance Score (ECOG PS) performance status 0-2

          -  Normal organ and marrow function as outlined in the protocol

          -  Left ventricular ejection fraction >/= 50%, as determined by radionuclide
             ventriculography (RVG) or echocardiogram within 60 days prior to initiation of
             protocol therapy

          -  Prior carboplatin is allowed if it was not given in conjunction with bevacizumab

          -  Prior trastuzumab is allowed

          -  No prior bevacizumab since diagnosis of CNS metastases or within 6 months prior to
             diagnosis of CNS metastases

          -  Women of child-bearing potential and men must agree to use adequate contraception
             prior to study entry and for the duration of study participation

        Exclusion Criteria:

          -  Patients who have had chemotherapy within 14 days prior to entering the study, or
             those who have not recovered adequately from adverse events due to agents administered
             earlier

          -  Patients may not receive any concurrent investigational agents while on study

          -  Patients may not receive any cancer-directed concurrent therapy , such as concurrent
             chemotherapy, radiotherapy, or hormonal therapy while on study. Concurrent treatment
             with bisphosphonates is allowed

          -  History of Grade 3 or 4 allergic reactions attributed to compounds of similar or
             identical biologic composition to bevacizumab, carboplatin, or trastuzumab

          -  Known contraindication to MRI with gadolinium contrast, such as cardiac pacemaker,
             shrapnel, or ocular foreign body

          -  Leptomeningeal carcinomatosis as the only site of CNS involvement

          -  More than 2 seizures over last 4 weeks prior to study entry

          -  Grade 1 or higher CNS hemorrhage on baseline brain MRI

          -  History of grade 2 or higher CNS hemorrhage within 12 months of study entry

          -  Inadequately controlled hypertension

          -  Prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infraction or unstable angina within 6 months prior to day 1

          -  Significant vascular disease within 6 months prior to day 1

          -  History of hemoptysis within 1 month prior to day 1

          -  Evidence of bleeding diathesis or significant coagulopathy

          -  Current, ongoing treatment with full-dose warfarin or its equivalent

          -  Use of aspirin (>325 mg/day) within 10 days prior to day 1

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to day 1 or anticipation of need for major surgical procedure during the course
             of the study.

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to day 1

          -  History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             day 1

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria as demonstrated by a urine protein-creatinine ratio >/= 1.0 at screening

          -  Known hypersensitivity to any component of bevacizumab

          -  Pregnancy or lactation