A Phase II Therapeutic Trial of the Use of Dabrafenib and Trametinib in Patients With BRAF V600 Mutation Positive Lesions in Erdheim Chester Disease

• Patients can be previously or simultaneously enrolled in the natural history ECD protocol #11-HG-0207, Clinical and Basic Investigations into Erdheim Chester disease. Eligible patients must have been diagnosed with Erdheim Chester disease, confirmed by pathological evaluation of the affected tissue with adequate staining. Affected tissue must harbor the BRAF V600 mutation

• Patients must have measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors 1.1

• Prior treatment, involving interferon, anakinra, imatinib, steroids, chemotherapy with, but not limited to cladribine, vinblastine, 6-mercaptopurine and etoposide, or other medications used empirically for the treatment of ECD, will be acceptable. These therapies should have been completed and discontinued 4 weeks or for biologic agents 4 weeks or 5 half-lives (whichever comes shorter) prior to enrollment in this study

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

⁃ Exception will be made for patients with ECOG performance status =\< 3 and Karnofsky performance scale \>= 50%, who require the use of wheelchairs, walkers or canes as well as assistance with daily routines secondary to disabilities caused by ECD cerebellar or brain disease that has been stable for \>= 3 months

• Life expectancy of greater than 3 months

• Able to swallow and 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 must have BRAF V600 mutation in the tumor tissue and/or cell-free deoxyribonucleic acid (DNA), identified by a Clinical Laboratory Improvement Act (CLIA)-certified lab

• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L

• Hemoglobin \>= 8 g/dL

• Platelets \>= 75 x 10\^9/L

• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN) except subjects with known Gilbert's syndrome

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN

• Serum creatinine =\< 1.5 x institutional ULN

• Left ventricular ejection fraction \>= institutional lower limit of normal (LLN) by echocardiogram (ECHO)

• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration or randomization

• Pregnancy and breast feeding. The effects of dabrafenib and trametinib on the developing human fetus are unknown. For this reason women of child-bearing potential must agree to use adequate contraception (barrier method of birth control, or abstinence; hormonal contraception is not allowed due to drug-drug interactions which can render hormonal contraceptives ineffective) for the duration of study participation, and for at least 2 weeks after treatment with dabrafenib or for 4 months after dabrafenib in combination with trametinib. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Based on studies in animals, it is also known that dabrafenib may cause damage to the tissue that makes sperm. This may cause sperm to be abnormal in shape and size and could lead to infertility, which may be irreversible. Safety and efficacy of the combination of dabrafenib and trametinib in pediatric populations have not been investigated. Dabrafenib or trametinib-dabrafenib combination should not be administered to pediatric populations outside clinical trials

• Therapeutic level dosing of warfarin can be used with close monitoring of prothrombin time (PT)/international normalized ratio (INR) by the site. Exposure may be decreased due to enzyme induction when on treatment, thus warfarin dosing may need to be adjusted based upon PT/INR. Consequently, when discontinuing dabrafenib, warfarin exposure may be increased and thus close monitoring via PT/INR and warfarin dose adjustments must be made as clinically appropriate. Prophylactic low dose warfarin may be given to maintain central catheter patency

• Ability to understand and the willingness to sign a written informed consent document