Clinical Trials /

Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma

NCT02367859

Description:

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.

Related Conditions:
  • Ameloblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Dabrafenib</span> in Treating Patients With <span class="go-doc-concept go-doc-biomarker">BRAF</span> <span class="go-doc-concept go-doc-keyword">Mutated</span> Ameloblastoma

Title

  • Brief Title: Dabrafenib in Treating Patients With BRAF Mutated Ameloblastoma
  • Official Title: A Pilot Study of Dabrafenib for Patients With BRAF Mutated Ameloblastoma
  • Clinical Trial IDs

    NCT ID: NCT02367859

    ORG ID: ENT0043

    NCI ID: NCI-2015-00169

    Trial Conditions

    Ameloblastoma

    BRAF Gene Mutation

    Trial Interventions

    Drug Synonyms Arms
    Dabrafenib BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436, Tafinlar Treatment (dabrafenib)

    Trial Purpose

    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 Description

    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.

    Trial Arms

    Name Type Description Interventions
    Treatment (dabrafenib) Experimental Patients receive dabrafenib PO 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. Dabrafenib

    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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Response rate according to RECIST version (v)1.1

    Secondary Outcome Measures

    Percent tumor necrosis

    Change in percent proliferation index by Ki67 immunohistochemistry

    Change in expression of phosphorylation of MEK and ERK by immunohistochemistry

    Trial Keywords

    ameloblastoma

    BRAF

    odontogenic cancer

    adamantinoma