2nd Line Treatment With Pemetrexed and Sorafenib for Recurrent or Metastatic Triple Negative Breast Cancer

This is an interventional treatment trial for Breast Cancer focused on measuring ER-negative, PgR-negative, Human epidermal growth factor receptor 2 (HER2-negative), Triple Negative Breast Cancer, HER2-negative Read More

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 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, which must be stable in the opinion of the investigator without a history of transfusion dependence.
• 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
• 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
• 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 in Section 6.7.11
• 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 (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
• QT interval, corrected (QTc) > 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 bpm or > 100 bpm, manual read of the QT interval by a cardiologist is required, with Fridericia correction applied to determine QT interval with correction using Fridericia's formula (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 (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
• 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 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

  *Note: Examples of clinical inducers of cytochrome p450 (CYP) isozymes and classification of strong, moderate, and weak interactions are available through the FDA website (Table 3-3 of website:): http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm

• Immunosuppressants (eg, 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 and 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