Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Gemcitabine, and Bevacizumab in Treating Patients With Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: bevacizumab; gemcitabine hydrochloride; paclitaxel albumin-stabilized nanoparticle formulation
Intervention MeSH terms: Paclitaxel; Bevacizumab; Gemcitabine; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; male breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as gemcitabine and 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 block tumor growth in different ways. Some block the ability of tumor cells
      to grow and spread. Others find tumor cells and help kill them or carry tumor-killing
      substances to them. Giving combination chemotherapy together with bevacizumab may kill more
      tumor cells.

      PURPOSE: This phase II trial is studying how well giving paclitaxel albumin-stabilized
      nanoparticle formulation and gemcitabine together with bevacizumab works in treating patients
      with metastatic breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or cytologically confirmed infiltrating breast cancer

               -  Clinical evidence of metastatic disease

          -  Measurable disease, defined as at least one measurable lesion per RECIST criteria

               -  No non-measurable disease only, defined as all other lesions, including small
                  lesions (longest diameter < 2 cm) and truly non-measurable lesions, including any
                  of the following:

                    -  Bone lesions

                    -  Leptomeningeal disease

                    -  Ascites

                    -  Pleural/pericardial effusion

                    -  Inflammatory breast disease

                    -  Lymphangitis cutis/pulmonis

                    -  Abdominal masses that are not confirmed and followed by imaging techniques

                    -  Cystic lesions

          -  Patients with HER-2/neu positive tumors, must have received prior treatment with
             trastuzumab (Herceptin®) or have a contraindication for trastuzumab

          -  No evidence of active brain metastasis, including leptomeningeal involvement, on MRI
             or CT scan

               -  CNS metastasis controlled by prior surgery and/or radiotherapy allowed

                    -  Must be asymptomatic for ≥ 2 months with no evidence of progression prior to
                       study entry

          -  Hormone receptor status not specified

        PATIENT CHARACTERISTICS:

          -  Menopausal status not specified

          -  Life expectancy ≥ 12 weeks

          -  ECOG performance status 0-1

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin ≥ 9.0 g/dL

          -  AST and ALT ≤ 2.5 times upper limit of normal (ULN)

          -  Alkaline phosphatase ≤ 2.5 times ULN

          -  Total bilirubin ≤ 1.5 times ULN

          -  Creatinine ≤ 1.5 mg/dL

          -  Urine protein:creatinine ratio < 1 or urinalysis < 1+ protein

               -  Patients discovered to have ≥ 1+ proteinuria at baseline must demonstrate 24-hour
                  urine protein < 1 g

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 30 days after
             completion of study therapy

          -  Able to complete questionnaires alone or with assistance

          -  No peripheral neuropathy > grade 1

          -  No history of allergy or hypersensitivity to albumin-bound paclitaxel, paclitaxel,
             gemcitabine hydrochloride, bevacizumab, albumin, drug product excipients, or
             chemically similar agents

          -  No stage III or IV invasive, non-breast malignancy within the past 5 years

          -  No other active malignancy, except nonmelanoma skin cancer or carcinoma in situ of the
             cervix

               -  Patient must not be receiving other specific treatment for a prior malignancy

          -  No uncontrolled hypertension (i.e., blood pressure [BP] > 160/90 mm Hg on ≥ 2
             occasions at least 5 minutes apart)

               -  Patients who have recently started or adjusted antihypertensive medications are
                  eligible providing that BP is < 140/90 mm Hg on any new regimen for ≥ 3 different
                  observations in ≥ 14 days

          -  No bleeding diathesis or uncontrolled coagulopathy

          -  No hemoptysis within the past 6 months

          -  No prior arterial or venous thrombosis within the past 12 months

          -  No history of cerebrovascular accident

          -  No history of hypertensive crisis or hypertensive encephalopathy

          -  No abdominal fistula or gastrointestinal perforation within the past 6 months

          -  No serious non-healing wound, ulcer, or fracture

          -  No clinically significant cardiac disease, defined as any of the following:

               -  Congestive heart failure

               -  Symptomatic coronary artery disease

               -  Unstable angina

               -  Cardiac arrhythmias not well controlled with medication

               -  Myocardial infarction within the past 12 months

          -  No comorbid systemic illnesses or other severe concurrent disease which, in the
             judgment of the investigator, would make the patient inappropriate for study entry or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No prior chemotherapy for metastatic disease

               -  May have received one prior adjuvant chemotherapy regimen

          -  Prior neoadjuvant chemotherapy allowed

               -  More than 6 months since prior adjuvant or neoadjuvant taxane (i.e., docetaxel or
                  paclitaxel) therapy

          -  Prior hormonal therapy in either adjuvant or metastatic setting allowed

          -  More than 4 weeks since prior radiotherapy (except if to a non-target lesion only, or
             single dose radiation for palliation)

               -  Prior radiotherapy to a target lesion is allowed provided there has been clear
                  progression of the lesion since radiotherapy was completed

          -  More than 4 weeks since prior cytotoxic chemotherapeutic agent or investigational drug

          -  More than 2 weeks since prior and no concurrent acetylsalicylic acid, anticoagulants,
             or thrombolytic agents (except for once-daily 81 mg acetylsalicylic acid)

          -  More than 6 weeks since prior major surgery, chemotherapy, or immunologic therapy

          -  More than 1 week since prior minor surgery (e.g., core biopsy)

               -  Placement of a vascular access device within 7 days is allowed

          -  More than 3 months since prior neurosurgery

          -  No concurrent treatment in a different clinical study in which investigational
             procedures are performed or investigational therapies are administered

               -  Trials related to symptom management (Cancer Control) which do not employ
                  hormonal treatments or treatments that may block the path of the targeted agents
                  used in this study may be allowed