Bevacizumab in Combination With Vinorelbine and Trastuzumab for HER2-Positive, Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: bevacizumab; vinorelbine; trastuzumab
Intervention description: Given intravenously every 2 weeks; Given intravenously once a week; Given intravenously once a week
Intervention MeSH terms: Bevacizumab; Trastuzumab; Vinorelbine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2 positive; bevacizumab; vinorelbine; trastuzumab

Summary:

      The purpose of this research study is to determine the effects of the combination of
      bevacizumab, vinorelbine, and trastuzumab on participants and their cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed invasive breast cancer, with metastatic
             disease.

          -  HER2-positive tumor

          -  Measurable disease defined as at least one lesion that can be accurately measured in
             at least one dimension as 20mm or greater with conventional techniques or as 10mm or
             greater with spiral CT scan

          -  18 years of age or older

          -  Life expectancy of more than 12 weeks

          -  ECOG Performance Status of 0 or 1

          -  Normal organ and marrow function as outlined in the protocol

          -  Left ventricular ejection fraction 50% or greater as determined by RVG or
             echocardiogram within 30 days prior to initiation of protocol therapy

          -  Patients with stable or previously treated CNS metastases are eligible for study
             participation, provided there is no history of clinically significant CNS bleeding

          -  Men and women of child-bearing potential must agree to use adequate contraception
             prior to study entry and for the duration of study participation

        COHORT A:

          -  No prior chemotherapy for treatment of metastatic breast cancer

          -  May NOT have received prior treatment with trastuzumab for recurrent or metastatic
             breast cancer

          -  No prior vinorelbine for treatment of breast cancer

          -  No prior bevacizumab for treatment of breast cancer

          -  May have received prior radiation therapy and/or any number of lines of hormonal
             therapy

          -  Prior trastuzumab therapy in the adjuvant setting is also allowed, providing that
             relapse occured at least 12 months following the last dose

          -  Must have recovered from all reversible toxicities related to prior therapy and may
             not have any pre-existing treatment-related toxicities in excess of Grade 1. Patients
             must have stopped prior radiation therapy at least 7 days prior to beginning protocol
             treatment

        COHORT B:

          -  One prior line of chemotherapy for treatment of metastatic breast cancer or recurrence
             of breast cancer within 12 months of completion of adjuvant trastuzumab

          -  No prior vinorelbine for treatment of breast cancer

          -  No prior bevacizumab for treatment of breast cancer

          -  May have received prior radiation therapy and/or any number of lines of hormonal
             therapy

          -  Must have recovered from all reversible toxicities related to prior therapy and may
             not have any pre-existing treatment-related toxicities in excess of Grade 1. Patients
             must have stopped prior radiation therapy at least 7 days prior to beginning protocol
             treatment

        Exclusion Criteria:

          -  Patients who have had chemotherapy within 14 days prior to entering the study, ot
             those who have not recovered adequately from adverse events due to agents administered
             earlier

          -  Concurrent radiation therapy

          -  History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical
             or biologic composition as the agents used in this study

          -  Prior therapy with bevacizumab or vinorelbine

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in an experimental drug study other than a Genentech-sponsored
             bevacizumab cancer study

          -  Inadequately controlled hypertension

          -  Prior history of hypertensive crisis of hypertensive encephalopathy

          -  NHYA Grade II or greater congestive heart failure

          -  History of myocardial infarction of unstable angina within 6 months prior to study
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  Progressive or untreated CNS metastases

          -  Significant vascular disease within 6 months prior to study enrollment

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of vascular access
             device, within 7 days prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria at screening

          -  Pregnant or lactating

          -  Current and ongoing treatment with full-dose warfarin or its equivalent