Phase II Trial of Sorafenib and Paclitaxel for Measurable Metastatic HER2-Negative Breast Cancer
Phase II Trial of Sorafenib and Paclitaxel for Measurable Metastatic HER2-Negative Breast Cancer
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.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib tosylate twice daily on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 4 weeks.
DISEASE CHARACTERISTICS:
Inclusion criteria:
Histologically* confirmed breast cancer
Stage IV (metastatic) disease
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
Primary tumor or metastatic tumor HER2-negative, defined as the following:
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:
PATIENT CHARACTERISTICS:
Inclusion criteria:
Exclusion criteria:
Active or uncontrolled medical illness (e.g., active infection > CTCAE grade 2), including any of the following:
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
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