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Dabrafenib

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This study is a single-arm study that does not involve randomization or blinding, nor does it establish a parallel control group and uses external control.

Generic name: Dabrafenib mesylate capsules Dosage form: capsule Specifications: 50mg, calculated as C23H20F3N5O2S2 Usage: Orally The dose of dabrafenib is 150 mg twice daily (equivalent to a total daily dose of 300 mg), taken at least 1 hour before or 2 hours after a meal. If you miss a dose and it is less than 6 hours before the next dose, you should not take it.

Patients who undergo fenestrated decompression will be administered the drug for 8 weeks, with curettage performed between weeks 8 and 9. Patients undergoing curettage will continue to take dabrafenib preoperatively until a few hours before surgery, but ideally, patients will take dabrafenib within 12 hours before surgery.

Baihui Miao

Qing Li

This pilot clinical trial plans to carry out dabrafenib adjuvant therapy combined with lesion curettage after fenestrated decompressive surgery for BRAF mutation-positive multicystic ameloblastoma to explore the effectiveness of this therapy in preventing tumor recurrence, reducing or even avoiding postoperative deformity and dysfunction. effect. Based on this, we plan to launch a prospective clinical study of dabrafenib in the treatment of BRAF V600E ameloblastoma, verify the feasibility of drug treatment or drug-assisted treatment of ameloblastoma, and provide patients with a safer Effective new treatment options will benefit more patients.

Main purpose:

To verify the application value of dabrafenib, a targeted drug targeting BRAF V600E mutation, combined with fenestration decompression and tumor curettage therapy in the treatment of multicystic ameloblastoma. It is expected to provide patients with a new treatment option that improves curative effect, reduces postoperative tumor recurrence, and avoids postoperative deformity.

Secondary purpose:

Study of regional heterogeneity in BRAF V600E-mutant ameloblastoma. Provide new ideas for finding other effective treatments.

Overall research design This study is a single-center, single-arm exploratory study. It is planned to enroll 10 patients with BRAF V600E mutation-positive multicystic ameloblastoma. After signing the informed consent form, you can enter the study as a subject.

Subjects will receive the study drug dabrafenib immediately after window decompression surgery. They will take dabrafenib for at least 8 weeks. Lesion curettage will be performed within the 8th to 9th week. Preoperative imaging will check the tumor volume. zoomed out situation. Patients whose lesions are not completely curettaged may choose to resume the dose of dabrafenib they received immediately before surgery.

Exploration of Fenestration Decompression Combined With Dalafenib in the Treatment of BRAF Mutant Ameloblastoma

It is defined as the proportion of patients whose tumor volume has been reduced by 40% between treatment after fenestration decompression and before curettage, that is, the sum of the proportions of complete response (CR) and partial response (PR).

The time from tumor curettage to disease recurrence (local, regional or distant metastasis), whichever occurs first, is determined according to the investigator's assessment.

Shandong University

graduate student

Trametinib

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.

Alexander Colevas

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

PRIMARY OBJECTIVES:

I. To observe the response rate of ameloblastoma to dabrafenib and trametinib 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 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.

Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma

A Pilot Study of Dabrafenib and Trametinib for Patients With BRAF Mutated Ameloblastoma

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 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.

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.

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.

Novartis Pharmaceuticals

Stanford University

Professor of Medicine (Oncology) and Otolaryngology

Patients receive dabrafenib orally twice daily every 12 hours plus trametinib daily orally 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.

Treatment (Dabrafenib)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. A. Dimitrios Colevas, Professor of Medicine (Oncology)

Tumor Response

On the basis of futility due to study closure with inadequate accrual, post-surgical research specimens were not analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exploration of Fenestration Decompression Combined With Dalafenib in the Treatment of BRAF Mutant Ameloblastoma	NCT06264778	Ameloblastoma	Dabrafenib	18 Years - 65 Years	Shandong University
Exploration of Fenestration Decompression Combined With Dalafenib in the Treatment of BRAF Mutant Ameloblastoma	NCT06264778	Ameloblastoma	Dabrafenib	18 Years - 65 Years	Shandong University
Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma	NCT02367859	Ameloblastoma BRAF Gene Mutat...	Dabrafenib Trametinib	18 Years -	Stanford University

Spots Global Cancer Trial Database for ameloblastoma