Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma
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|ClinicalTrials.gov Identifier: NCT02367859|
Recruitment Status : Recruiting
First Posted : February 20, 2015
Last Update Posted : July 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Ameloblastoma BRAF Gene Mutation||Drug: Dabrafenib Other: Laboratory Biomarker Analysis 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)|
|Estimated Enrollment :||17 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|
|Estimated Primary Completion Date :||October 2019|
|Estimated Study Completion Date :||August 2020|
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: Laboratory Biomarker Analysis
Other Name: Mekinist
- Response rate according to RECIST version (v)1.1 [ Time Frame: 6 weeks ]RECIST v1.1 response rate
- Percent tumor necrosis [ Time Frame: At the time of endpoint biopsy or surgical resection ]Routine Hematoxylin and Eosin slide review will measure extent of tumor necrosis. Percentage of tumor necrosis by volume assessed. The biopsy slide of the resection specimen examined and the volume of the necrosis compared to the volume of the total tumor determined by the centrally reviewing pathologists and percentage readouts of tumor necrosis, in increments of 10%, will be determined. In addition to measuring tumor necrosis the slide review will estimate therapy effect on intact cells by estimating the percent cells with therapy-associated nuclear atypia.
- Change in percent proliferation index by Ki67 immunohistochemistry [ Time Frame: Baseline to time of endpoint biopsy or surgical resection ]Proliferation index evaluation will be performed in the laboratory on the initial pre-treatment biopsy and either the endpoint biopsy or the resection specimen. Ki-67 immunohistochemistry will be scored by at least two pathologists using percentage positive cells as the primary metric. The results of the immunohistochemical analysis will be expressed as both raw data in addition to a ratio between pre- and post- treatment.
- Change in expression of phosphorylation of MEK and ERK by immunohistochemistry [ Time Frame: Baseline to time of endpoint biopsy or surgical resection ]Immunohistochemistry evaluation for MEK/ERK will be performed on the initial pre-treatment biopsy and either the endpoint biopsy or the resection specimen. Immunohistochemistry will be scored by at least two pathologists using percentage positive cells and intensity of staining as the primary metrics. The results of the immunohistochemical analysis will be expressed as both raw data in addition to a ratio between pre- and post- treatment.
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
|Contact: Elizabeth Wintersfirstname.lastname@example.org|
|United States, California|
|Stanford University, School of Medicine||Recruiting|
|Stanford, California, United States, 94305|
|Contact: Elizabeth Winters 650-721-6509 email@example.com|
|Principal Investigator: Alexander D. Colevas|
|Sub-Investigator: Jonathan Pollack|
|Sub-Investigator: Davud Sirjani|
|Sub-Investigator: Robert West|
|Principal Investigator:||Alexander Colevas||Stanford University|