Sorafenib and Paclitaxel in Treating Patients With Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: paclitaxel; sorafenib tosylate
Intervention description: The chemotherapy drug called paclitaxel (Taxol) treats breast cancer, lung cancer, ovarian cancer and Kaposis sarcoma; Sorafenib is a type of targeted therapy known as a kinase inhibitor used to treat advanced renal cell carcinoma and unresectable hepatocellular carcinoma
Intervention MeSH terms: Paclitaxel; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; male breast cancer; recurrent breast cancer; HER2-negative breast cancer

Summary:

      RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy,
      such as paclitaxel, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Giving sorafenib together with
      paclitaxel may kill more tumor cells.

      PURPOSE: This phase II trial is studying the side effects of giving sorafenib together with
      paclitaxel and to how well it works in treating patients with metastatic breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

        Inclusion criteria:

          -  Histologically* confirmed breast cancer

               -  Stage IV (metastatic) disease

                    -  Radiographic evidence of metastases NOTE: *Histological confirmation of the
                       actual metastasis is not required.

          -  Measurable disease by RECIST criteria defined as ≥ 1 unidimensionally measurable
             lesion ≥ 20 mm by conventional techniques (i.e., physical examination, CT scan, MRI,
             or x-ray) or ≥ 10 mm by spiral CT scan

               -  No prior radiotherapy unless growth has been documented following radiotherapy

          -  Primary tumor or metastatic tumor HER2-negative, defined as the following:

               -  Immunohistochemistry of 0 or 1+ OR the equivalent, if an automated quantitative
                  assay is used

               -  HER2 fluorescent in situ hybridization (FISH) assay negative as defined by a
                  HER2:chromosome 17 centromeric probe ratio < 1.8 (or < 2.2 if
                  immunohistochemistry is less than 3+ or equivalent) OR equivalent values for
                  negative FISH assays that do not normalize to chromosome 17

          -  Hormone-receptor positive (estrogen receptor-[ER] or progesterone receptor
             [PgR]-positive) disease or hormone receptor-negative (ER- or PgR-negative) disease

          -  Tumor block from initial breast cancer primary or a biopsy of a metastatic site must
             be available for correlative studies

          -  Brain metastases allowed provided the patient is stable after completion of treatment
             (i.e., surgery and/or radiotherapy), asymptomatic, and off steroids with 2 consecutive
             stable brain scans at least 4 weeks after radiotherapy

        Exclusion criteria:

          -  Bone-only or other nonmeasurable-only disease

          -  Newly diagnosed brain metastases

        PATIENT CHARACTERISTICS:

        Inclusion criteria:

          -  ECOG performance status 0-1

          -  Life expectancy > 6 months

          -  Menopausal status not specified

          -  WBC ≥ 3,000/mcL

          -  Absolute neutrophil count ≥ 1,500/mcL

          -  Platelets ≥ 100,000/mcL

          -  Total bilirubin < 1.5 times upper limit of normal (ULN)

          -  AST and ALT transaminases ≤ 2.5 times ULN (< 5 times ULN if liver involvement)

          -  Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min

          -  INR < 1.5 OR PT/PTT normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception prior to and during (women and men)
             and for at least 3 months after (men) study therapy

          -  Able to swallow and absorb oral medications

        Exclusion criteria:

          -  Active or uncontrolled medical illness (e.g., active infection > CTCAE grade 2),
             including any of the following:

               -  HIV or chronic hepatitis B or C

               -  Uncontrolled diabetes

               -  NYHA class II-IV uncompensated congestive heart failure

               -  Unstable angina (anginal symptoms at rest)

               -  New onset angina (i.e., began within the past 3 months)

               -  Coronary artery disease

          -  Myocardial infarction within the past 6 months

          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

          -  Evidence of bleeding diathesis or coagulopathy

          -  Pulmonary hemorrhage/bleeding event > CTCAE grade 2 within 4 weeks of first dose of
             study drug

          -  Any other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of first study drug

          -  Thrombotic or embolic events (i.e., cerebrovascular accident), including transient
             ischemic attacks within the past 6 months

          -  Hypertension that cannot be controlled with medication to ≤ 150/90 mm Hg

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to sorafenib tosylate

          -  Prior invasive cancer other than breast cancer except nonmelanoma skin cancer

          -  Chronic nonhealing wound or ulcer

        PRIOR CONCURRENT THERAPY:

          -  No more than 1 prior chemotherapy regimen for metastatic breast cancer (MBC)

          -  At least 3 weeks since prior hormonal therapy for MBC or adjuvant or neoadjuvant
             chemotherapy

               -  More than 1 year since adjuvant paclitaxel

          -  At least 4 weeks since major thoracic, abdominal, or pelvic surgery and recovered

          -  At least 3 weeks since prior and no concurrent investigational drugs

          -  Concurrent bisphosphonates allowed

          -  Concurrent anticoagulation agents (i.e., warfarin or heparin) allowed

          -  No anticipated need for or concurrent radiotherapy

          -  No concurrent Hypericum perforatum (St. John wort) or rifampin (rifampicin)

          -  No other concurrent anti-neoplastic drugs