Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Metastatic Triple-Negative Breast Cancer

Inclusion Criteria:

Patients must have histologically or cytologically confirmed metastatic invasive breast cancer that is negative for the estrogen receptor (ER), progesterone receptor (PR) and HER2 by institutional guidelines
Patients must have measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1])
Patients must have had exposure to at least 1 and no more than 3 prior chemotherapy regimens for the treatment of metastatic breast cancer
Patients must consent to both a pretreatment and a post-treatment mandatory research biopsy prior to enrolling on trial, and therefore, must have tissue (excluding bone or brain) that is amenable to biopsy
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Life expectancy of greater than 3 months
Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
All prior treatment-related toxicities must be Common Terminology Criteria for Adverse Events version 4 (CTCAE v4) grade =< 1 (except alopecia) at the time of enrollment
Absolute neutrophil count >= 1,500/mcL
Platelets >= 75,000/mcL
Total bilirubin =< 1.5 × institutional upper limit of normal
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA)
Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
Patients must have controlled blood pressure with a systolic blood pressure < 140 mmHg and diastolic < 90 mmHg; anti-hypertensive medications are permitted
Patients must be at least 4 weeks from last radiation dose; patients must be at least 4 weeks from last chemotherapy, targeted therapy, or biologic therapy (exception allowed for a 2 week washout for patients who were on chemotherapy at less than a standard of care dose, as long as all other eligibility criteria are met); patients must be at least 4 weeks from last surgical procedure and recovered from all post-operative complications
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of trametinib monotherapy or in combination with GSK2141795 administration
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

History of another malignancy

Exception: patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible
History of interstitial lung disease or pneumonitis
History of type I diabetes mellitus; if a patient has type II diabetes, they must have a hemoglobin (hemoglobin A1C) =< 8%; patients with a screening fasting glucose > 120 mg/dL will be excluded
Uncontrolled hypothyroidism; patients must have a normal thyroid-stimulating hormone (TSH) per institutional standards at baseline
Patients who are receiving any other investigational agents
Individuals with symptomatic or progressive brain metastases are ineligible; subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for >= 3 weeks after completion of local therapy; any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for >= 3 weeks prior to study enrollment
History of allergic reactions attributed to compounds of similar chemical or biologic composition to trametinib monotherapy or trametinib in combination with GSK2141795

Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:

Other anti-cancer therapy while on study treatment (megestrol if used as an appetite stimulant is allowed)
The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], gingko biloba, yohimbe, saw palmetto, or ginseng)
Patients receiving strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, history of hyperviscosity or hypercoagulability syndromes; visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study, breastfeeding should be discontinued if the mother is treated with trametinib monotherapy or trametinib in combination with GSK2141795
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible