Dabrafenib and Trametinib in People With BRAF V600E Mutation Positive Lesions in Erdheim Chester Disease
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|ClinicalTrials.gov Identifier: NCT02281760|
Recruitment Status : Completed
First Posted : November 4, 2014
Results First Posted : June 7, 2021
Last Update Posted : August 31, 2021
|Condition or disease||Intervention/treatment||Phase|
|BRAF V600E Mutation||Drug: Dabrafenib Mesylate Drug: Trametinib Dimethyl Sulfoxide||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Therapeutic Trial of the Use of Dabrafenib and Trametinib in Patients With BRAF V600E Mutation Positive Lesions in Erdheim Chester Disease|
|Study Start Date :||November 1, 2014|
|Actual Primary Completion Date :||August 29, 2018|
|Actual Study Completion Date :||August 29, 2018|
Experimental: Combination therapy with dabrafenib and trametinib in patients with ECD
Patients with Erdheim Chester Disease (ECD) and BRAFV600E mutation received combination therapy with dabrafenib, a BRAFV600E inhibitor 150mg orally every twelve hours, and trametinib, an inhibitor of MEK, downstream of BRAF, 2mg orally daily.
Drug: Dabrafenib Mesylate
Description: Dabrafenib mesylate (GSK2118436B) is a potent and selective BRAF kinase inhibitor. This inhibition suppresses downstream activity of pERK, a biomarker, and has antiproliferative activity against BRAF mutant tumors.The mode of action is consistent with ATP competitive inhibition.
Drug: Trametinib Dimethyl Sulfoxide
Trametinib dimethyl sulfoxide is a reversible, highly selective, allosteric inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. Tumor cells commonly have hyperactivated extracellular signal-related kinase (ERK) pathways in which MEK is a critical component. Trametinib dimethyl sulfoxide inhibits activation of MEK by RAF kinases and MEK kinases.
- Number of Participants With Partial Response to Dabrafenib and Trametinib [ Time Frame: 24 months ]Efficacy of dabrafenib and trametinib as combination therapy in patients with BRAFV600E positive Erdheim Chester Disease based on RECIST 1.1 criteria of a partial response greater than or equal to 30% decrease in at least one target lesion size.
- Number of Participants With Adverse Events to Dabrafenib and/or Trametinib [ Time Frame: 24 months ]Safety of dabrafenib and trametinib as combination therapy, or either drug as single-agent therapy among participants, as measured by the adverse event characteristics of participants. See the adverse event table for list of specific adverse events experienced.
- Clinical Response Rate to Dabrafenib/Trametinib Combination Therapy in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease. [ Time Frame: 24 months ]Clinical response rate to dabrafenib and trametinib combination therapy in patients as measured by the percentage of patients who met RECIST 1.1 criteria for a partial response.
- Progression-free Survival in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease [ Time Frame: 24 months ]Progression free survival rate using RECIST 1.1 criteria among participants during the entire study period of 24 months. Progression is defined as a 20% increase in the diameter of target lesions, or a significant increase in a non-target lesion, or the appearance of new lesions.
- Overall Survival in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease [ Time Frame: 24 months ]Overall survival rate among participants defined as the number of patients alive at the end of the 24-month study period.
- Disease Resistance to Dabrafenib/Trametinib Combination Therapy in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease [ Time Frame: 12 months ]Disease resistance to the combination therapy during the active treatment phase of the study. Resistance is defined as evidence of disease progression per RECIST 1.1 in a participant previously exhibiting stable disease or at least a partial response according to RECIST 1.1 criteria. Also, disease progression is defined as the requirement of dosage escalation in order to maintain current efficacy.
- Time Response to Dabrafenib/Trametinib Combination Therapy in a Cohort of Patients With BRAFV600E Positive Erdheim Chester Disease. [ Time Frame: 12 months ]Time to response to combination therapy defined as the minimum length of time elapsed during the active treatment phase to reach at least a partial response, as defined by RECIST 1.1 criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02281760
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||William A Gahl, M.D.||National Human Genome Research Institute (NHGRI)|