Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer

Inclusion Criteria

• •PHASE I PORTION ELIGIBILITY CRITERIA:
• •Patients must have BRAF\^V600 mutant metastatic cancer irrespective of the histology or prior therapy; BRAF\^V600 mutant status must be documented by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; use of an Food and Drug Administration (FDA)-approved test is preferred although other BRAF tests at a CLIA-certified laboratory may also be accepted
• •Patients must have locally advanced unresectable stage IIIC or metastatic stage IV cancer with either progression to prior therapy or a newly diagnosed cancer that does not have an available treatment with curative intent
• •Patients must have a complete physical examination and medical history within 28 days prior to registration
• •Patients must have measurable or non-measurable disease; all measurable lesions must be assessed (by physical examination, computed tomography \[CT\], or magnetic resonance imaging \[MRI\] scan) within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; all disease must be assessed and documented on the baseline tumor assessment form (Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1)
• •All patients must undergo a CT or MRI of the brain within 42 days prior to registration; patients with asymptomatic brain metastases or previously treated brain metastases that are stable (i.e. not requiring corticosteroids) at the time of registration will be eligible
• •Patients may have received prior systemic therapy (chemotherapy, immunotherapy, biologic therapy, or combination regimens); all adverse events associated with prior treatment must have resolved to \< grade 1 prior to registration
• •Patients progressing on a prior BRAF inhibitor-based therapy will be eligible, as are patients naive to BRAF inhibitor therapy; resistance to BRAF inhibitor-based therapy will be defined as progressive disease by RECIST 1.1 criteria while receiving therapy with a BRAF inhibitor (vemurafenib or dabrafenib, alone or in combination with a mitogen-activated protein kinase \[MEK\] inhibitor); this may be innate resistance (patients who never achieved a tumor response while on BRAF inhibitor therapy) or acquired resistance (progression after having a tumor response to BRAF inhibitor therapy); there will not be a period of break between progression on the prior BRAF inhibitor-based therapy and the start of dabrafenib, trametinib and GSK2141795
• •Patients may have received prior surgery (for both the primary and stage IV disease); all adverse events associated with prior surgery must have resolved to =\< grade 1 prior to registration
• •Patients may have received prior radiation therapy; all adverse events associated with prior radiation therapy must have resolved to =\< grade 1 prior to registration
• •Patients must be willing to submit blood for pharmacokinetics; sites must order S1221 pharmacokinetic (PK) kit immediately after registration; the Southwest Oncology Group (SWOG) patient identification (ID) number must be provided on the S1221 PK Kit request form
• •Patients must have available and be willing to submit baseline tissue taken at the time of disease progression to prior BRAF inhibitor-based therapy (either fresh frozen \[preferred\], or paraffin-embedded tumor blocks) OR must have a site of disease that can be biopsied within this study for translational medicine studies; tissue may be from an archival biopsy or a new biopsy after the patient has been registered to the protocol; since patients are referred to this protocol after progression on prior BRAF inhibitor-based therapy, the biopsy taken at the time of progression will be used as the baseline biopsy for this study; patients must be willing to submit plasma and whole blood for translational medicine studies
• •Patients must have Zubrod performance status =\< 1
• •Absolute neutrophil count (ANC) \>= 1,200/ul (obtained within 28 days prior to registration)
• •Platelets \>= 100,000/ul (obtained within 28 days prior to registration)
• •Hemoglobin \>= 9 g/dL (obtained within 28 days prior to registration)
• •Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (or =\< 2.5 x ULN for patients with Gilbert's syndrome) (with 28 days prior to registration)
• •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (or \< 5 x IULN for patients with known liver metastases) (obtained within 28 days prior to registration)
• •Serum albumin \>= 2.5 g/dL (obtained within 28 days prior to registration)
• •Serum creatinine =\< 1.5 mg/dL OR measured or calculated creatinine clearance \>= 50 mL/min (obtained within 28 days prior to registration)
• •Patient must have a left ventricular ejection fraction \>= institutional lower limit of normal (LLN) by echocardiogram (ECHO) or multigated acquisition (MUGA) within 28 days prior to registration
• •Patients with melanoma must have a serum lactate dehydrogenase (LDH) test performed within 28 days prior to registration
• •Patients receiving anticoagulation treatment are allowed to participate with international normalized ratio (INR) established within the therapeutic range
• •Women of childbearing potential must have a negative pregnancy test within 14 days of registration
• •Patients must be able to retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels; patients who have feeding tubes can enroll in the study provided that the capsules do not need to be modified
• •Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• •As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• •Patients must be \>= 18 years of age
• •Patients must have a serum albumin \>= 2.5 g/dL within 28 days prior to registration
• •PHASE II PORTION ELIGIBILITY CRITERIA:
• •Patients must have histologically confirmed melanoma with BRAF\^V600 mutation; patients must have stage IIIC or stage IV disease
• •Patients must have received prior BRAF inhibitor therapy (e.g. dabrafenib, vemurafenib) within 56 days prior to registration; prior trametinib therapy is permitted; patients are not required to interrupt BRAF or MEK inhibitor therapy prior to the initiation of three agent combination therapy on study
• •Patients must have measurable disease; all measurable lesions must be assessed (by physical examination, CT, or MRI scan) within 28 days prior to registration; tests to assess non-measurable disease must be performed within 42 days prior to registration; patients whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration; all disease must be assessed and documented on the baseline tumor assessment form (RECIST 1.1)
• •Patients must have Zubrod performance status =\< 2