Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma
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|ClinicalTrials.gov Identifier: NCT02367859|
Recruitment Status : Completed
First Posted : February 20, 2015
Results First Posted : January 21, 2020
Last Update Posted : January 21, 2020
|Condition or disease||Intervention/treatment||Phase|
|Ameloblastoma BRAF Gene Mutation||Drug: Dabrafenib Drug: Trametinib||Phase 2|
I. To observe the response rate of ameloblastoma to dabrafenib and trametinib at 6 weeks.
I. Feasibility and safety in this patient population. II. Response will be assessed pathologically. III. Two main histologic assays for treatment response will be used: tumor necrosis and phosphorylated-mitogen-activated protein kinase kinase 1 (MEK), phosphorylated-extracellular signal-regulated kinase (ERK), and Ki-67 levels as measured by immunohistochemistry.
Patients receive dabrafenib orally (PO) twice daily (BID) every 12 hours and trametinib 2 mg daily PO for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients whose disease is judged to be not amenable to resection will continue dabrafenib and trametinib indefinitely as long as there has not been tumor progression.
After completion of study treatment, patients are followed up for at least 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Dabrafenib and Trametinib for Patients With BRAF Mutated Ameloblastoma|
|Actual Study Start Date :||July 17, 2017|
|Actual Primary Completion Date :||November 5, 2018|
|Actual Study Completion Date :||June 26, 2019|
Experimental: Treatment (dabrafenib)
Patients receive dabrafenib PO BID every 12 hours plus trametinib daily PO for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients whose disease is judged to be not amenable to resection will continue dabrafenib and trametinib indefinitely as long as there has not been tumor progression.
Other Name: Mekinist
- Tumor Response [ Time Frame: 6 weeks ]
Tumor response was assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Overall tumor response was assessed as the number of participants achieving either a complete response (CR) or a partial response (PR). The criteria are:
- CR = Disappearance of all target lesions
- PR = ≥ 30% decrease in the sum of the longest diameter of target lesions
- Overall Response (OR) = CR + PR
- Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
- Stable disease (SD) = Small changes that do not meet any of the above criteria
The outcome is reported as the number of participants achieving the different levels of tumor response per RECIST, a number without dispersion.
- Percent Tumor Necrosis [ Time Frame: 6 weeks ]Percent of tumor necrosis at the time of endpoint biopsy or surgical resection will be assessed. The tumor specimen from resection will be examined and the volume of the necrosis compared to the volume of the total tumor determined by central pathology. Percent tumor necrosis, in increments of 10%, will be determined. The outcome will be reported as the mean percent tumor necrosis, with standard deviation.
- Change in Proliferation [ Time Frame: 6 weeks ]An immunohistochemical laboratory analysis to assess proliferation will be performed on the initial pre-treatment biopsy (baseline) vs either the endpoint tumor biopsy or the tumor specimen from the resection. Ki-67 immunohistochemistry will be scored by at least 2 pathologists using percentage positive cells as the primary metric. Proliferation will be assessed as the difference from baseline in Ki-67 labeling to the end of treatment (tumor biopsy or the tumor specimen). The outcome will be expressed as the mean, with standard deviation.
- Phosphorylation of Tumor Markers MEK and ERK [ Time Frame: 6 weeks ]An immunohistochemical laboratory analysis to assess phosphorylation of the tumor markers MEK and ERK on the initial pre-treatment biopsy (baseline) vs either the endpoint tumor biopsy or the tumor specimen from the resection. Immunohistochemistry will be scored by at least 2 pathologists using percentage positive cells and intensity of staining as the primary metrics. Phosphorylation of MEK and ERK will be assessed as the observed difference in phosphorylated MEK and ERK labeling from baseline to the end of treatment (tumor biopsy or the tumor specimen). The outcome will be expressed as the mean, with standard deviation.
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): NCT02367859
|United States, California|
|Stanford University, School of Medicine|
|Stanford, California, United States, 94305|
|Principal Investigator:||Alexander Colevas||Stanford University|