Inclusion Criteria
- Unresectable breast cancer involving chest wall, regional nodes, or distant site
- Breast cancer determined to be ER-negative and PgR-negative defined for this study as
< 10% tumor staining by IHC (Note: Eligibility should be based on the ER and PgR
status reported at the time of the most recent biopsy or resection).
- Breast cancer determined to be HER2-negative per current American Society of Clinical
Oncologists/College of American Pathologists (ASCO/CAP) HER2 Guidelines (Note:
Eligibility should be based on the HER2 status reported at the time of the most
recent biopsy or resection).
- Disease progression during or after treatment for recurrent or metastatic disease
- A minimum of 1 previous chemotherapy regimen for treatment of recurrent or metastatic
disease
- Measurable disease per RECIST v1.1
- Age 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Ability to swallow oral medications
- Adequate bone marrow function as defined below:
- Absolute neutrophil count (ANC) 1,200/mm3
- Platelet count 100,000/mm3
- Hemoglobin 9.0 g/dL (untransfused)
- Adequate renal function as defined below:
- Calculated creatinine clearance 45 mL/min
- Adequate hepatic function as defined below:
- Total bilirubin 1.5 x upper limit of normal (ULN) for the laboratory
- Aspartate aminotransferase (AST) 3 x ULN for the laboratory, except in the presence
of known hepatic metastasis, wherein the AST may be 5 x ULN
- Alanine aminotransferase (ALT) 3 x ULN for the laboratory, except in the presence
of known hepatic metastasis, wherein the ALT may be 5 x ULN
- International normalized ratio (INR) 1.5
- Serum B12 and folate levels lower limit of normal (LLN) for the laboratory (Note:
Patients may begin B12 and folic acid supplementation and be reconsidered for
participation in the study when levels are LLN for the laboratory).
- Ability to take folic acid, vitamin B12, and dexamethasone according to the protocol
instructions
- Ability to interrupt chronic non-steroidal anti-inflammatory drugs (NSAIDs) beginning
2 days before (5 days before for long-acting NSAIDs) and continuing for 2 days
following administration of pemetrexed
- Toxicities from previous cancer therapies resolved to grade 1 unless specified
otherwise in the inclusion or exclusion criteria (Exception: Neuropathy related to
previous chemotherapy must be resolved to grade 2.)
- Women who are not postmenopausal or have not undergone hysterectomy must have a
documented negative serum pregnancy test within 7 days prior to initiating study
treatment. Note: Postmenopausal is defined as one or more of the following:
- Age 60 years
- Age < 60 years and amenorrheic for at least 1 year with follicle-stimulating hormone
(FSH) and plasma estradiol levels in the postmenopausal range
- Bilateral oophorectomy
- A woman of child-bearing potential (WCBP) must agree to use a medically accepted
method for preventing pregnancy for the duration of study treatment and for 2 months
following completion of study treatment.
- Ability to understand and willingness to sign the consent form written in English
Exclusion Criteria
- Any investigational agent within 4 weeks prior to initiating study treatment
- Known or presumed intolerance of pemetrexed or sorafenib
- Known or suspected malabsorption condition or obstruction
- Symptomatic or untreated brain metastases (Note: Patients with known brain metastases
who are asymptomatic and have had post-treatment imaging that indicates stable
disease in the brain are eligible. Also, note that imaging of the brain is required
within 8 weeks prior to study registration).
- Any documented history of clinically identifiable thrombotic, embolic, venous, or
arterial events such as cerebrovascular accident, transient ischemic attack, deep
vein thrombosis, or pulmonary embolism within 6 months prior to initiating study
treatment (Note: Patients with a tumor-associated thrombus of locally-involved
vessels or with incidental asymptomatic filling defects identified on imaging are not
excluded).
- Contraindication to antiangiogenic agents, including:
- Serious non-healing wound, non-healing ulcer, or bone fracture
- Major surgical procedure or significant traumatic injury within 4 weeks prior to
initiating study treatment
- Pulmonary hemorrhage/bleeding event grade 2 (CTCAE v4.0) within 12 weeks prior to
initiating study treatment
- Any other hemorrhage/bleeding event grade 3 (CTCAE v4.0) within 12 weeks prior to
initiating study treatment
- Systolic blood pressure (BP) > 160 mmHg or diastolic BP > 100 mmHg despite optimal
medical management
- QTcF interval > 450 ms ( grade 1) on electrocardiogram (ECG)
- If baseline QTcF on screening ECG is grade 1:
- Check potassium and magnesium serum levels
- Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm
exclusion of patient due to QTcF
- For patients with heart rate < 60 bpm or > 100 bpm, manual read of the QT interval by
a cardiologist is required, with Fridericia correction applied to determine QTcF
(Note: If heart rate is 60-100 bpm, manual read of QTcF is not required).
- Active or clinically significant cardiac disease including any of the following:
- Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months
prior to initiating study treatment
- Myocardial infarction within 6 months prior to initiating study treatment
- Ventricular arrhythmias requiring anti-arrhythmic therapy other than beta blockers
- New York Heart Association (NYHA) class III or IV congestive heart failure
- Serious (ie, grade 3) uncontrolled infection
- Uncontrolled effusion (Note: Patients with small effusions remaining after
pleurodesis are eligible. Determination of eligibility based on pleural size will be
determined by the principal investigator).
- Known human immunodeficiency virus (HIV) seropositivity (Note: HIV testing is not
required)
- Chronic or active hepatitis B or C infection requiring treatment with antiviral
therapy
- Seizure disorder requiring enzyme-inducing anti-epileptic drugs (EIAEDs) (Note: If
the seizure disorder can be managed with agents that are not EIAEDs (eg,
levetiracetam or valproate), the patient should not be excluded).
- Planned ongoing administration of a STRONG CYP3A4 inducer (Note: The reference list
of cytochrome p450 (CYP) isozymes and classification of strong, moderate, and weak
interactions is available through the FDA website).
- Pregnancy or breastfeeding
- Diagnosis or treatment for another malignancy within 3 years of enrollment, with the
following exceptions: complete resection of basal cell carcinoma or squamous cell
carcinoma of the skin, any in situ malignancy, and low-risk prostate cancer after
curative therapy
- Medical, psychological, or social condition that, in the opinion of the investigator,
may increase the patient's risk or limit the patient's adherence with study
requirements
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both