Clinical Trial: Dabrafenib in Treating Patients With BRAF Mutated Ameloblastoma

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Pilot Study of Dabrafenib for Patients With BRAF Mutated Ameloblastoma

Brief Summary: This pilot clinical trial studies dabrafenib in treating patients with ameloblastoma and a specific mutation (change) in the BRAF gene. Dabrafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To observe the response rate of ameloblastoma to dabrafenib at 6 weeks.

SECONDARY OBJECTIVES:

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.

OUTLINE:

Patients receive dabrafenib orally (PO) twice daily (BID) every 12 hours 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 indefinitely as long as there has not been tumor progression.

After completion of study treatment, patients are followed up for at least 4 weeks.

Current Primary Outcome: Response rate according to RECIST version (v)1.1 [ Time Frame: 6 weeks ]

Original Primary Outcome: Response rate according to RECIST version (v)1.1 [ Time Frame: 6 weeks ]

Current Secondary Outcome:

• 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.

Original Secondary Outcome: Same as current

Information By: Stanford University

Dates:
Date Received: February 13, 2015
Date Started: April 2017
Date Completion: April 2020
Last Updated: March 1, 2017
Last Verified: March 2017