Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer
Condition: Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: paclitaxel albumin-stabilized nanoparticle formulation; bevacizumab; erlotinib hydrochloride
Intervention description: Given IV; Given IV; Given PO
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Erlotinib Hydrochloride; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: Female
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving paclitaxel albumin-stabilized nanoparticle
      (Nab-paclitaxel) formulation together with bevacizumab followed by bevacizumab and erlotinib
      hydrochloride work in treating patients with metastatic breast cancer. Drugs used in
      chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Monoclonal antibodies, such as bevacizumab, can prevent cancer growth by
      blocking the ability of cancer cells to grow and spread. Erlotinib hydrochloride may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial
      evaluates a maintenance treatment with erlotinib and bevacizumab after Nab-paclitaxel and
      bevacizumab which may control cancer growth with biologic therapies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have histologically confirmed invasive breast cancer that is estrogen receptor (ER)
             negative (=< 10%), progesterone receptor (PR) negative (=< 10%) and human epidermal
             growth factor receptor 2 (HER2) normal (=< 10% of cells) by immunohistochemistry (IHC)
             or fluorescence in situ hybridization (FISH)

          -  Be receiving first-line therapy for metastatic disease

          -  Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria;
             X-rays, scans or physical examinations used for tumor measurement must have been
             completed within 28 days prior to registration; X-rays, scans or other tests for
             assessment of non-measurable disease must have been performed within 42 days prior to
             registration

          -  OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29
             or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at
             least 14 days apart with the most recent measurement being within 42 days prior to
             registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20%
             increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40
             units/mL or for CEA be greater than or equal to 4 ng/mL

          -  Subjects with brain metastases as their first site of disease recurrence may be
             eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain)
             with clinically controlled neurologic symptoms for a period of 21 days prior to study
             treatment

          -  Bilirubin =< 1.5 mg/dL

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper
             limit of normal, unless bone metastasis is present in the absence of liver metastasis

          -  Alkaline phosphatase =< 2.5 X upper limit of normal, unless bone metastasis is present
             in the absence of liver metastasis

          -  Platelets > 100,000 cells/mm^3

          -  Hemoglobin > 9.0 g/dL

          -  Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

          -  Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable

          -  If of childbearing potential must have a negative pregnancy test and use an effective
             method to avoid pregnancy for the duration of the trial and for at least 6 months
             after completion of study therapy

          -  Pre-existing peripheral neuropathy, if present, must be < grade 2 (per Common
             Terminology Criteria for Adverse Events [CTCAE] version 3.0)

          -  Patients must be informed of the investigational nature of this study and must sign
             and give informed consent in accordance with institutional standards and federal
             guidelines

        Exclusion Criteria:

          -  Recurrent disease within 12 months after completion of adjuvant chemotherapy
             containing a weekly taxane

          -  Central nervous system (CNS) metastases that are symptomatic and/or requiring steroids

          -  Pre-existing nephritic syndrome

          -  Serious intercurrent medical or psychiatric illness including serious active infection

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or
             diastolic blood pressure > 100 mmHg on antihypertensive medications)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) grade II or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

          -  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 a 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, ulcer, or bone fracture

          -  Proteinuria at screening as demonstrated by either:

               -  Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR

               -  Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria
                  on dipstick urinalysis at baseline must have a UPC ratio done that is < 1.0 to be
                  eligible; if the UPC ratio is >= 1.0 then the patient should undergo a 24-hour
                  urine collection which must demonstrate =< 1 g of protein in 24 hours for the
                  patient to be eligible)

          -  Known hypersensitivity to any component of bevacizumab or to nab-paclitaxel
             (paclitaxel albumin-stabilized nanoparticle formulation)