Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma
Condition: Ameloblastoma; BRAF Gene Mutation
MeSH terms: Ameloblastoma; Adamantinoma
Intervention: Dabrafenib; Trametinib
Intervention description: Given PO; Given PO
Intervention MeSH terms: Trametinib; Dabrafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ameloblastoma; BRAF; odontogenic cancer; adamantinoma

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological diagnosis of ameloblastoma; all stages are eligible; patients must have
             evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria

          -  B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E or other known dabrafenib
             sensitive BRAF mutation in tumor by any Clinical Laboratory Improvement Amendments
             (CLIA) certified lab; may include, for example, Sanger sequencing, SNaPshot platform,
             immunohistochemistry, Foundation One tests, etc.)

          -  Life expectancy > 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          -  Absolute neutrophil count (ANC) > 1.5 x10^9/L

          -  Platelet (PLT) > 99 x 10^9/L

          -  Hemoglobin > 8 g/dL

          -  Total bilirubin (Tbili) < 1.6 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.6 x ULN

          -  Alkaline phosphatase (alk phos) < 2.6 x ULN

          -  Serum creatinine < 1.6 x ULN or creatinine clearance > 50 ml/min

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Patients of childbearing potential must agree to use effective contraception until at
             least 6 months after treatment with dabrafenib

          -  Able to swallow and retain oral medication and must not have any clinically
             significant gastrointestinal abnormalities that may alter absorption such as
             malabsorption syndrome or major resection of the stomach or bowels

          -  Left ventricular ejection fraction equal to or greater than normal

        Exclusion Criteria:

          -  No prior treatment with agents targeting BRAF mutant tyrosine kinases or radiation of
             target lesions

          -  Invasive malignancy other than ameloblastoma within 3 years, excluding curatively
             treated basal cell carcinoma, and other highly curable cancers such as early stage
             cutaneous squamous cell carcinoma (T1 NO) cervical carcinoma in situ (CIS), early
             stage prostate cancer, thyroid cancer or breast cancer

          -  Uncontrolled hypertension, chronic heart failure (CHF), or other major medical illness

          -  Prior allergic reactions attributed to compounds of similar chemical or biologic
             composition to dabrafenib

          -  Concomitant use of strong inhibitors (e.g., ketoconazole, nefazodone, clarithromycin,
             gemfibrozil) or strong inducers (e.g., rifampin, phenytoin, carbamazepine,
             phenobarbital, St John's wort) of cytochrome P450, family 3, subfamily A, polypeptide
             4 (CYP3A4) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8)

          -  Concomitant use of proton pump inhibitors, H2-receptor antagonists, antacids

          -  Known glucose-6-phosphate dehydrogenase (G6PD) deficiency

          -  Pregnant or nursing patients; women of childbearing potential must have a negative
             pregnancy test within 14 days of enrollment

          -  Electrocardiogram (EKG) with QTcB (Bazett's formula) > 480 ms done within 14 days of
             enrollment

          -  Interstitial lung disease or pneumonitis

          -  A history of retinal vein occlusion (RVO)

          -  Congestive heart failure NYHA class III or worse (Marked limitation of physical
             activity. Comfortable at rest. Less than ordinary activity causes fatigue,
             palpitation, or dyspnea.)

          -  A history of acute coronary syndromes (including myocardial infarction or unstable
             angina), coronary angioplasty, or stenting within 6 months