Second Line Treatment with Pemetrexed and Sorafenib for Recurrent or Metastatic Triple Negative Breast Cancer

Inclusion Criteria

• Unresectable adenocarcinoma of the breast involving chest wall, regional nodes, or distant site
• Breast cancer determined to be estrogen receptor (ER)-negative and progesterone receptor (PgR)-negative defined for this study as < 10% tumor staining by immunohistochemistry (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 Oncology/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
• At least one prior regimen for treatment of recurrent or metastatic disease * Note: Prior regimen for recurrent or metastatic disease is not required if the patient had disease progression or recurrence during or within the first 6 months following completion of adjuvant or neoadjuvant chemotherapy
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Ability to swallow oral medications
• Absolute neutrophil count (ANC) >= 1,200/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin >= 9.0 g/dL, which must be stable in the opinion of the investigator without a history of transfusion dependence
• Calculated creatinine clearance >= 45 mL/min
• 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
• 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 each pemetrexed dose
• Toxicities from previous cancer therapies resolved to =< grade 1 unless specified otherwise in the inclusion or exclusion criteria (Exceptions: Chronic residual toxicities that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profiles of pemetrexed and sorafenib, such as alopecia, changes in pigmentation, stable endocrinopathies; 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) and a male patient with partner who is a 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
• Anticancer therapy within 2 weeks prior to initiating study treatment
• Plans for concurrent anticancer therapy except as permitted
• Known or presumed intolerance of pemetrexed or sorafenib
• Known or suspected malabsorption condition or obstruction
• Brain metastases meeting either of the following exclusion criteria: * Untreated brain metastases * After completion of brain-directed therapy, the patient has not been able to tolerate discontinuation of steroids or a decrease in steroid dose
• Leptomeningeal metastasis
• 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 an asymptomatic catheter-related thrombus or 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 (Common Terminology Criteria for Adverse Events [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
• Corrected QT (QTc) interval > 480 ms (>= grade 2) on a 12-lead electrocardiogram (ECG) * If baseline QTc on screening ECG is >= grade 2: ** Check potassium and magnesium serum levels ** Correct any identified hypokalemia and/or hypomagnesemia and repeat ECG to confirm exclusion of patient due to QTc * For patients with heart rate < 60 beats per minute (bpm) or > 100 bpm, manual read of the QT interval by a cardiologist is required, with Fridericia correction applied to determine Fridericia QTc (QTcF) which must be used to determine eligibility * Note: If heart rate is 60-100 bpm, manual read of the QT interval and correction to QTcF is not required
• Active or clinically significant cardiac disease including any of the following: * Unstable angina (e.g., 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 (i.e., >= grade 3) uncontrolled infection
• Uncontrolled effusion e.g., presence of third space fluid that, in the opinion of the investigator, cannot be successfully controlled by drainage * 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 (e.g., levetiracetam or valproate), the patient should not be excluded
• Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the study drugs; if such drugs have been used, patients must have discontinued these agents at least 2 weeks (or as noted below) prior to initiating study treatment; examples include: * STRONG CYP3A4 inducers * Immunosuppressants (e.g., tacrolimus, leflunomide, tofacitinib, roflumilast, pimecrolimus) * NSAIDs ** Note: NSAIDs must be discontinued within 5 days prior to initiating study treatment
• Pregnancy or breastfeeding
• Previous malignancy with the following exceptions: adequately treated basal cell carcinoma or squamous cell carcinoma of the skin; any in situ malignancy; adequately treated stage 1 or stage 2 cancer from which the patient is currently in remission; any other cancer from which the patient has been disease-free for 3 years
• 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