This phase II trial studies the side effects and how well dabrafenib and trametinib work in treating patients with Erdheim Chester disease that have BRAF V600 gene mutations. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Name: Dabrafenib Mesylate
Description: Given POType: DrugTreatment (dabrafenib mesylate, trametinib dimethyl sulfoxide)
Name: Quality-of-Life Assessment
Description: Ancillary studiesType: OtherTreatment (dabrafenib mesylate, trametinib dimethyl sulfoxide)
Name: Questionnaire Administration
Description: Ancillary studiesType: OtherTreatment (dabrafenib mesylate, trametinib dimethyl sulfoxide)
Name: Trametinib Dimethyl Sulfoxide
Description: Given POType: DrugTreatment (dabrafenib mesylate, trametinib dimethyl sulfoxide)
Description: Measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Response to therapy will be evident on follow up imaging studies revealing a decrease in lesion size of 30% or more, which is defined as a partial response as per RECIST criteria, when compared to baseline studies.
Measure: Clinical response rate Time: Up to 48 weeks after completion of study treatmentDescription: Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Measure: Incidence of toxicities Time: Up to 48 weeks after completion of study treatmentDescription: Will be reported using Kaplan-Meier curves and appropriate 95% confidence intervals.
Measure: Time to response Time: Up to 48 weeks after completion of study treatmentDescription: Will be reported using Kaplan-Meier curves and appropriate 95% confidence intervals.
Measure: Duration of response Time: From the time measurement criteria are met for complete or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 48 weeks after completion of study treatmentDescription: Will be reported using Kaplan-Meier curves and appropriate 95% confidence intervals.
Measure: Progression-free survival Time: From start of treatment to time of progression or death, whichever occurs first, assessed up to 48 weeks after completion of study treatmentDescription: Will be reported using Kaplan-Meier curves and appropriate 95% confidence intervals.
Measure: Overall survival Time: Up to 48 weeks after completion of study treatmentDescription: Patients will be evaluated using the multi-dimensional fatigue inventory.
Measure: Change in fatigue Time: Baseline up to 48 weeks after completion of study treatmentDescription: Patients will be evaluated using the 6 minute walk test, single leg stance, and functional reach and grip strength using a dynamometer.
Measure: Change in level of functioning Time: Baseline up to 48 weeks after completion of study treatmentDescription: Patients will be evaluated using the human activity profile and activity card sort.
Measure: Change in ability to perform routine activities Time: Baseline up to 48 weeks after completion of study treatmentDescription: Patients will be evaluated using the comparative pain scale.
Measure: Change in pain Time: Baseline up to 48 weeks after completion of study treatmentDescription: Patients will be evaluated using the the group peg board test.
Measure: Change in fine motor dexterity Time: Baseline up to 48 weeks after completion of study treatmentDescription: Improvement of patients' overall quality of life will be evidence of response, and assessments will be made at baseline and throughout the trial, as well as at the conclusion of the trial, to evaluate for any improvement in quality of life. Patients will be evaluated using the National Institute of Neurological Disorders and Stroke-Neuro-Quality of Life scale.
Measure: Change in overall quality of life Time: Baseline up to 48 weeks after completion of study treatmentDescription: Resistance to therapy will be evaluated through imaging studies and patient follow up for at least one year, but this is not expected with the combination therapy.
Measure: Resistance to therapy Time: Up to 1 yearSingle Group Assignment
There is one SNP
These potential risks may also apply to other agents used in this study - History of retinal vein occlusion (RVO) - Interstitial lung disease or pneumonitis not secondary to ECD - Central serous retinopathy (CSR) including presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or visible pathology (e.g., evidence of optic disc cupping, evidence of new visual field defects on automated perimetry, or intraocular pressure > 21 mmHg as measured by tonography) as assessed by ophthalmic examination - Inability to travel to the treating center - Patients with confirmed diagnosis of ECD that are asymptomatic and with no visceral involvement are not eligible for this trial (patients with no target lesions as per RECIST 1.1 criteria) BRAF NP_004324.2:p.V600X Erdheim-Chester Disease Erdheim-Chester Disease PRIMARY OBJECTIVES: I. To study the efficacy and safety of dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) as combination therapy in patients with BRAF V600E positive Erdheim Chester disease. --- V600E ---
To determine the clinical response rate to dabrafenib and trametinib combination therapy in patients with BRAF V600E positive Erdheim Chester disease. --- V600E ---
V. To establish duration of treatment-endpoints in patients with BRAF V600E positive Erdheim-Chester disease (ECD) lesions. --- V600E ---