Docetaxel With Bevacizumab as First-Line Therapy in Treating Women With Stage IV Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: bevacizumab; Docetaxel
Intervention description: Patients receive bevacizumab 15 mg/kg intravenously (I.V.) every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal.; docetaxel: 75 mg/m2 IV q3 weeks. Subjects continue on dosing until they experience unacceptable toxicity, disease progression, or withdrawal of patient consent.
Intervention MeSH terms: Bevacizumab; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; recurrent breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as docetaxel, 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. Bevacizumab may also stop the growth of tumor
      cells by stopping blood flow to the tumor. It is not yet known whether giving docetaxel
      together with bevacizumab is more effective than docetaxel alone in treating breast cancer.

      PURPOSE: This randomized phase II trial is studying how well giving docetaxel together with
      bevacizumab works compared to docetaxel alone as first-line therapy in treating women with
      stage IV breast cancer.
    

Eligibility criteria:

        Inclusion Criteria

          -  Female 18 and over

          -  Histologically or cytologically confirmed adenocarcinoma of the breast at first
             diagnosis

          -  Stage IV disease, with at least one measurable lesion according to the RECIST
             criteria.

          -  HER2-negative disease, by fluorescence in situ hybridization

          -  ECOG performance status 0-1

          -  Life expectancy of at least 24 weeks

          -  No prior chemotherapy for metastatic breast cancer (prior endocrine therapy is
             permitted).

          -  Prior adjuvant chemotherapy is permitted. If patients received a taxane in the
             adjuvant setting, at least 12 months must have elapsed since the completion of
             adjuvant therapy.

          -  At least 4 weeks since prior surgery, radiotherapy, endocrine therapy, or experimental
             drug therapy, with complete recovery from the effects of these interventions

          -  If female of childbearing potential, pregnancy test is negative and willing to use
             effective contraception while on treatment for at least 3 months thereafter.

          -  Patient is accessible and willing to comply with treatment and follow-up.

          -  Patient is willing to provide written informed consent prior to the performance of any
             study-related procedures.

          -  Required laboratory values

               -  Absolute neutrophil count ≥ 1,500/mm^3

               -  Platelet count ≥ 100,000/mm^3

               -  Hemoglobin ≥ 9.0 g/dL

               -  Creatinine ≤ 2.0 mg/dL

               -  Total bilirubin < 1.0 x upper limit of normal (ULN) (patients with documents
                  Gilbert's syndrome are eligible).

               -  Alkaline phosphatase (AP) normal AND Angiotensin Aspartate Aminotransferase (AST)
                  or Alanine Aminotransferase (ALT) ≤ 2.5 times upper limit of normal (ULN) or AP ≤
                  2.5 times ULN AND AST or ALT ≤ 1.5 times ULN or AP ≤ 5 times ULN AND AST or ALT
                  normal.

        Exclusion Criteria

          -  Prior chemotherapy for metastatic breast cancer

          -  Prior treatment with an anti-angiogenic agent

          -  Concurrent therapy with any other non-protocol anti-cancer therapy

          -  Current or prior history of central nervous system or brain metastases

          -  Presence of neuropathy > grade 2 (NCI- Common Toxicity Criteria (CTC) version 3.0) at
             baseline

          -  Presence of any non-healing wound, fracture, or ulcer, or the presence of clinically
             significant (> grade 2) peripheral vascular disease

          -  History of any other malignancy within the past 5 years, with the exception of
             non-melanoma skin cancer or carcinoma-in-situ of the cervix

          -  Clinically significant cardiovascular disease (e.g., uncontrolled hypertension [BP >
             150/100]), myocardial infarction or stroke within the past 6 months, unstable angina,
             New York Heart Association (NYHA) Grade II or greater congestive heart failure, or
             serious cardiac arrhythmia requiring medication

          -  Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal
             condition increasing the risk of perforation; history of abdominal fistula,
             gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to
             beginning therapy

          -  Active, uncontrolled infection requiring parenteral antimicrobials

          -  The presence of any other medical or psychiatric disorder that, in the opinion of the
             treating physician, would contraindicate the use of the drugs in this protocol or
             place the subject at undue risk for treatment complications.

          -  Inability to comply with the study protocol or follow-up procedures

          -  Pregnancy or lactation

          -  A history of a severe hypersensitivity reaction to Bevacizumab, or Docetaxel or other
             drugs formulated with polysorbate 80.

          -  Evidence of bleeding diathesis or coagulopathy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to beginning therapy, or anticipation of the need for a major surgical procedure
             during the course of the study; minor surgical procedure, fine needle aspiration or
             core biopsy within 7 days prior to beginning therapy

          -  Proteinuria at baseline or clinically significant impairment of renal function.
             Subjects unexpectedly discovered to have > 1+ proteinuria at baseline should undergo a
             24 hour urine collection, which must be an adequate collection and must demonstrate <1
             gm of protein/24 hour to allow participation in the study.