Phase I/II Trial of Sorafenib Plus Ixabepilone in HER2-Negative Metastatic Breast Cancer

Inclusion Criteria

• Age ≥ 18 years.
• Histologically or cytologically confirmed breast cancer diagnosis

with metastatic disease. Patients without pathologic or cytologic

confirmation of metastatic disease should have unequivocal

evidence of metastasis.

• Measurable disease, as per RECIST criteria (Therasse et al.

2000). Measurable disease cannot be previously irradiated

unless progression was documented. Measurable disease is

defined as: at least one lesion that can be accurately measured in

at least one dimension [longest diameter to be recorded] as

>20 mm with conventional techniques, or as >10 mm with spiral

computed tomography (CT) scan. Disease must be measurable,

i.e., bone-only disease or evaluable-only disease is not eligible.

• Patients with brain metastasis may participate if they:
• have undergone appropriate treatment,
• are at least 1 month post-treatment,
• have no neurologic symptoms,
• are not on steroids,
• have a follow-up magnetic resonance imaging (MRI) scan that

demonstrates no residual active lesions, and

• have no new untreated lesions.

5 The following prior therapies are allowed:

• No prior chemotherapy in the metastatic setting. However,

patients must have received prior adjuvant or neo-adjuvant

chemotherapy.

• Prior radiation therapy in either the metastatic or early-stage

setting, as long as 4 weeks before initiation of

study treatment is allowed.

6 HER2-negative status. Documentation of HER2 results must be

available at the time of study enrollment. HER2-negative is

defined as:

• Immunohistochemical (IHC) 0 or IHC 1+ OR
• Fluorescence in situ hybridization (FISH) negative (defined by

FISH ratio 1,500/μL;

• platelets >100,000/μL;
• hemoglobin >9 g/dL.

9 Normal hepatic function as defined by:

• total bilirubin within normal institutional limits;
• aspartate aminotransferase (AST) and alanine

aminotransferase (ALT) 6 months.

• For women of childbearing potential, negative serum pregnancy

test within 7 days prior to starting treatment.

• For women of childbearing potential and men, agreement to use a

method of contraception that is acceptable to their physician from

time of first signing the informed consent and for the study

duration. Men should use adequate birth control for at least three

months after the last administration of sorafenib. If a woman

becomes pregnant or suspects she is pregnant while participating

in this study, she must agree to inform her treating physician

immediately. As applicable, patients must agree to discontinue

breast-feeding until at least 3 weeks after their last dose of study

drug.

• Recovery to 1) prior chemotherapy regimen.
• Treatment with chemotherapy, biologic agents, or targeted agents

within the previous 4 weeks.

• Previous treatment with sorafenib or ixabepilone.
• Women who are pregnant or breastfeeding.
• Neuropathy (motor or sensory) greater than grade 1.
• Uncontrolled intercurrent illness including (but not limited to)

ongoing or active infection >grade 2.

• Known history of human immunodeficiency virus (HIV), Hepatitis

B, or Hepatitis C infection.

• History of other non-breast cancer malignancy treated with

curative intent within the 5 years preceding study enrollment with

the exception of carcinoma in situ of the cervix, non-melanoma

skin cancer, or follicular thyroid cancer.

• Concurrent hormonal therapy, chemotherapy other than

ixabepilone, or radiation treatments while on study as well as

treatment with other investigational agents while on study.

• Cardiac disease:

•Congestive heart failure (CHF) greater than New York Heart Association

(NYHA) Class II (see Appendix B).

• Unstable angina (anginal symptoms at rest) or new onset angina

(i.e., began within the last 3 months).

• Myocardial infarction within the past 6 months.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension (systolic blood pressure >150 mmHg

or diastolic pressure >10