A Pilot Study of Dabrafenib and Trametinib for Patients With BRAF Mutated Ameloblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Tumor Response
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Dabrafenib (Drug)
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.
干预措施: Trametinib (Drug)
结局指标
主要结局
Tumor Response
时间窗: 6 weeks
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.
次要结局
- Percent Tumor Necrosis(6 weeks)
- Change in Proliferation(6 weeks)
- Phosphorylation of Tumor Markers MEK and ERK(6 weeks)
研究者
A. Dimitrios Colevas
Professor of Medicine (Oncology) and Otolaryngology
Stanford University