Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction

Inclusion Criteria

• •Patients must have a histologically or cytologically confirmed solid malignancy that is metastatic or unresectable for which standard curative or palliative treatments do not exist or are no longer effective
• •* Hepatocellular carcinoma (HCC) patients are not required to have histologically or cytologically confirmed malignancy, patients are considered eligible based on tumor markers and/or imaging assessment
• •* Based on recent data that have shown limited trametinib benefit, patients with the following tumor types will be excluded from the normal and mild cohorts:
• •* Pancreatic cancer patients
• •* Colorectal cancer patients
• •* BRAF V600E melanoma patients who have failed BRAF inhibitors
• •* Note: Patients with pancreatic cancer, colorectal cancer, and BRAF V600E melanoma patients who have failed BRAF inhibitors are allowed to enroll in the moderate and severe cohorts provided the patients: 1) sign a separate consent form which outlines the extremely limited activity observed in prior studies, and 2) are consented to the study by a protocol-specified designee who is not their longitudinal oncologist
• •All patients must have completed any prior chemotherapy, targeted therapy, radiotherapy (unless palliative doses which must be discussed with study principal investigator), surgery, anti-angiogenic therapy or interferon \>= 28 days before study entry
• •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• •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 (CTCAE) version 4.0 grade =\< 1 (except alopecia) at the time of enrollment
• •Absolute neutrophil count (ANC) \>= 1.2 x 10\^9/L
• •Hemoglobin \>= 9 g/dL
• •Platelets \>= 75 x 10\^9/L
• •Serum creatinine =\< 1.5 mg/dL (=\< 133 umol/L) OR calculated creatinine clearance (Cockcroft-Gault formula) \>= 50 mL/min OR 24-hour urine creatinine clearance \>= 50 mL/min
• •Proteinuria =\< +1 on dipstick or =\< 1 gram/24 hours
• •Prothrombin time (PT) =\< 1.5 x institutional upper limit of normal (ULN)
• •International normalized ratio (INR) =\< 1.5 x institutional ULN
• •Partial thromboplastin time (PTT) =\< 1.5 x institutional ULN
• •Left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
• •No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes
• •Patients with abnormal hepatic function will be eligible and will be grouped according to criteria summarized below:
• •* Group A: Normal hepatic function
• •* Bilirubin =\< ULN
• •* Aspartate aminotransferase (AST) =\< ULN
• •* Group B: Mild hepatic dysfunction
• •* B1: bilirubin =\< ULN and AST \> ULN
• •* B2: ULN \< bilirubin =\< 1.5 x ULN and any AST
• •* Group C: Moderate hepatic dysfunction
• •* 1.5 x ULN \< bilirubin =\< 3 x ULN and any AST
• •* Group D: Severe hepatic dysfunction
• •* 3 x ULN \< bilirubin =\< 10 x ULN and any AST; hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results
• •* Patients with active hemolysis should be excluded. No distinction should be made between liver dysfunction due to metastases and liver dysfunction due to other causes. Hepatic function tests should be repeated within 24 hours prior to starting initial therapy and may result in patients' group assignment being altered if different to registration test results
• •Trametinib can cause fetal harm when administered to a pregnant woman; 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, during the study participation, and for four months after the last dose of the drug; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to registration and agree to use effective contraception throughout the treatment period and for 4 months after the last dose of study treatment; 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
• •Ability to understand and the willingness to sign a written informed consent document
• •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
• •Animal reproductive studies have not been conducted with trametinib; therefore, the study drug must not be administered to pregnant women or nursing mothers; women of childbearing potential should be advised to avoid pregnancy and use effective methods of contraception; men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception; if a female patient or a female partner of a patient becomes pregnant while the patient receives trametinib, the potential hazard to the fetus should be explained to the patient and partner (as applicable)
• •HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• •Any condition or medical problem in addition to the underlying malignancy and organ dysfunction which the investigator feels would pose unacceptable risk