中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2400080725
最近更新日期： Date of Last Refreshed on：	2024-02-05 16:19:13
注册时间： Date of Registration：	2024-02-05 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	开窗减压术联合达拉非尼治疗BRAF突变型成釉细胞瘤探索研究
Public title：	Exploration of fenestration decompression combined with dalafenib in the treatment of BRAF mutant ameloblastoma
注册题目简写：
English Acronym：
研究课题的正式科学名称：	开窗减压术联合达拉非尼治疗BRAF突变型成釉细胞瘤探索研究
Scientific title：	Exploration of fenestration decompression combined with dalafenib in the treatment of BRAF mutant ameloblastoma
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	庙百慧	研究负责人：	李青
Applicant：	Baihui Miao	Study leader：	Qing Li
申请注册联系人电话： Applicant telephone：	+86 188 4572 7762	研究负责人电话： Study leader's telephone：	+86 152 8885 2318
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	18845727762@163.com	研究负责人电子邮件： Study leader's E-mail：	lq580202@hotmail.com
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	山东省济南市历下区文化西路44-1号	研究负责人通讯地址：	山东省济南市历下区文化西路44-1号
Applicant address：	No. 44-1, Wenhua West Road, Lixia District, Jinan City, Shandong Province	Study leader's address：	No. 44-1, Wenhua West Road, Lixia District, Jinan City, Shandong Province
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	山东大学口腔医院
Applicant's institution：	School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University
研究负责人所在单位：	山东大学口腔医院
Affiliation of the Leader：	School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	20231106	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	山东大学口腔医院伦理委员会
Name of the ethic committee：	Ethics Committee of Stomatology Hospital of Shandong University
伦理委员会批准日期： Date of approved by ethic committee：	2023-11-23 00:00:00
伦理委员会联系人：	吕艾芹
Contact Name of the ethic committee：	Aiqin Lv
伦理委员会联系地址：	山东省济南市历下区文化西路44-1号
Contact Address of the ethic committee：	No. 44-1, Wenhua West Road, Lixia District, Jinan City, Shandong Province
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 159 6662 5205	伦理委员会联系人邮箱： Contact email of the ethic committee：

研究实施负责（组长）单位：

山东省口腔医院（山东大学口腔医院）

Primary sponsor：

Stomatological Hospital of Shandong University

研究实施负责（组长）单位地址：

山东省济南市历下区文化西路44-1号

Primary sponsor's address：

No. 44-1, Wenhua West Road, Lixia District, Jinan City, Shandong Province

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	山东	市(区县)：	济南
Country：	China	Province：	Shandong	City：	Jinan
单位(医院)：	山东大学口腔医院	具体地址：	山东省济南市历下区文化西路44-1号
Institution hospital：	Stomatological Hospital of Shandong University	Address：	No. 44-1, Wenhua West Road, Lixia District, Jinan City, Shandong Province

经费或物资来源：

自筹

Source(s) of funding：

Self financing

研究疾病：

成釉细胞瘤

Target disease：

Ameloblastoma

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

探索性研究/预试验

Study phase：

0

研究设计：

单臂

Study design：

Single arm

研究目的：

主要目的：验证针对BRAF V600E突变的靶向药物达拉非尼与开窗减压术联合应用，并配合肿瘤刮除术疗法，在多囊型成釉细胞瘤治疗方面的应用价值。有望为患者提供一种提高疗效、减少肿瘤术后复发且避免术后畸形全新疗法选择。次要目的：研究BRAF V600E突变成釉细胞瘤区域异质性。为寻找其他有效治疗方式提供新的思路。

Objectives of Study：

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.

药物成份或治疗方案详述：

本研究通过开窗减压术与BRAF抑制剂达拉非尼联合应用，探索该疗法在BRAF突变的多囊型成釉细胞瘤治疗方面的作用。预计招募10例符合纳入标准的受试者，开展前瞻性、单臂探索研究。研究分析开窗减压术配合达拉非尼在肿瘤刮治术前缩小肿瘤体积的疗效，以及探索该疗法在预防肿瘤复发、减轻乃至避免术后畸形与功能障碍方面的作用，并创新性应用单细胞测序与空间转录组技术，对服用达拉非尼前后患者肿瘤细胞类型、BRAF V600E表达情况及表达区域的空间分布的变化进行分析，进一步验证该治疗方案的有效性。并与既往单纯应用手术的治疗方式进行对比，发掘该疗法在BRAF突变的多囊型成釉细胞瘤肿瘤治疗上的优势与前景，为患者提供一种更为安全有效的全新治疗方案，并希望借此攻克成釉细胞瘤术后复发与畸形的难题。

Description for medicine or protocol of treatment in detail：

This study used fenestrated decompression combined with the BRAF inhibitor dabrafenib to explore the role of this therapy in the treatment of BRAF-mutated multicystic ameloblastoma. It is expected to recruit 10 subjects who meet the inclusion criteria to conduct a prospective, single-arm exploratory study. Study and analyze the efficacy of fenestrated decompression combined with dabrafenib in reducing tumor volume before curettage, and explore the role of this therapy in preventing tumor recurrence, reducing or even avoiding postoperative deformity and dysfunction, and applying it innovatively Single-cell sequencing and spatial transcriptome technology were used to analyze the changes in tumor cell types, BRAF V600E expression and the spatial distribution of expression regions in patients before and after taking dabrafenib to further verify the effectiveness of this treatment plan. And compared with the previous treatment methods that only use surgery, we will explore the advantages and prospects of this therapy in the treatment of BRAF-mutated polycystic ameloblastoma tumors, and provide patients with a new, safer and more effective treatment plan, and hope that this can overcome the problems of postoperative recurrence and deformity of ameloblastoma.

纳入标准：

Inclusion criteria

(1) Histology confirmed ameloblastoma.
(2) The patient was tested positive for BRAF V600E mutation.
(3) Eligible patients must have evaluable lesions within the jaw that meet RECIST criteria.
(4) Aged 18 or above.
(5) Laboratory test results:
ANC > 1.5 x 109/L
PLT > 99 x 109/L
Hemoglobin >8 g/dL
Tbili < 1.6 × ULN
AST, ALT and alkaline phosphate < 2.6 times the upper limit of normal (ULN)
Serum creatinine ≤1.5 mg/dL, or serum creatinine >1.5 mg/dL, creatinine clearance must be ≥50ml/min
PR / INR, PTT ≤ 1.3 × ULN, patients receiving anticoagulation therapy can participate in the trial if their INR is within the therapeutic range before randomization.
(6) Patients of childbearing potential must agree to use effective contraception for at least 6 months after treatment with dabrafenib.
(7) Be able to swallow and retain oral medications and must not have any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or intestines.
(8) The left ventricular ejection fraction is equal to or greater than normal within 1 month of enrollment.
(9) Voluntarily sign the informed consent form and cooperate with the treatment.

排除标准：

（1）既往使用过BRAF抑制剂治疗者。（2）3年内患有除成釉细胞瘤以外的浸润性恶性肿瘤者，除外高治愈率的癌症，如早期皮肤鳞状细胞癌(T1 N0)、宫颈癌、早期前列腺癌、甲状腺癌、乳腺癌以及任何时间内确认有激活RAS突变的恶性肿瘤者。（3）过去或目前有视网膜静脉闭塞者。（4）具有间质性肺疾病或肺部炎症病史者。（5）患有未控制的高血压(收缩压> 140 mm Hg，舒张压> 90 mm Hg，不能通过降压治疗控制)、心力衰竭或其他严重内科疾病者。（6）与达拉非尼或曲美替尼化学或生物成分相似的化合物引起的既往过敏反应者。（7）同时服用强CYP3A4或CYP2C8抑制剂(如酮康唑、奈法唑酮、克拉霉素、吉非齐尔)或强诱导剂(如利福平、苯妥英、卡马西平、苯巴比妥)者。（8）同时服用质子泵抑制剂、H2受体拮抗剂、抗酸剂者。（9）已知G6PD缺乏者。（10）孕妇或哺乳期患者。有生育能力的妇女必须在入组后14天内血清妊娠试验呈阴性。有生育能力的妇女必须同意在入组前14天、整个治疗期间以及最后一剂研究治疗后的4至6个月内使用有效的避孕措施。（11）在入组14天内心电图QTcB > 480 ms者。（12）充血性心力衰竭NYHA III级或更严重(体力活动明显受限)者。（13）6个月内有急性冠状动脉综合征(包括心肌梗死或不稳定型心绞痛)、冠状动脉成形术或支架植入术史，或有超声心动图记录的当前有临床意义的不受控制的心律失常或心脏内除颤器或心脏瓣膜形态异常(≥2级)的病史或证据。1级异常(即轻度反流/狭窄)的受试者可入组。中度瓣膜增厚的受试者不符合条件。在给药前房颤控制> 30天的受试者是合格的。（14）既往全身性抗癌治疗(化疗、免疫治疗、生物治疗、研究治疗前3周内的疫苗治疗、或研究治疗前2周内无延迟毒性的化疗)者。（15）任何严重或不稳定的先前存在的疾病、精神疾病或其他可能影响受试者安全、获得知情同意或遵守研究程序的疾病。（16）乙型肝炎病毒(HBV)或丙型肝炎病毒(HCV)感染史。有HBV和/或HCV实验室证据已治愈的受试者将被允许。

Exclusion criteria：

(1) Those who have used BRAF inhibitor treatment in the past. (2) Patients with invasive malignant tumors other than ameloblastoma within 3 years, excluding cancers with high cure rates, such as early cutaneous squamous cell carcinoma (T1 N0), cervical cancer, early prostate cancer, thyroid cancer, and breast cancer Cancer and malignant tumors with confirmed activating RAS mutations at any time. (3) Those who have had retinal vein occlusion in the past or currently. (4) Those with a history of interstitial lung disease or lung inflammation. (5) Those suffering from uncontrolled hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, which cannot be controlled by antihypertensive treatment), heart failure or other serious medical diseases. (6) Patients with previous allergic reactions caused by compounds with similar chemical or biological components to dabrafenib or trametinib. (7) Taking strong CYP3A4 or CYP2C8 inhibitors (such as ketoconazole, nefazodone, clarithromycin, gemfizil) or strong inducers (such as rifampin, phenytoin, carbamazepine, phenobarbide) at the same time appropriate). (8) Those who take proton pump inhibitors, H2 receptor antagonists, and antacids at the same time. (9) People with known G6PD deficiency. (10) Pregnant or lactating patients. Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment. Women of childbearing potential must agree to use effective contraception 14 days before enrollment, throughout treatment, and for 4 to 6 months after the last dose of study treatment. (11) Those with electrogram QTcB > 480 ms within 14 days of enrollment. (12) Patients with congestive heart failure NYHA grade III or more severe (physical activity is significantly limited). (13) History of acute coronary syndrome (including myocardial infarction or unstable angina), coronary angioplasty or stent implantation within 6 months, or current clinically significant uncontrolled disease recorded by echocardiography History or evidence of arrhythmias or intracardiac defibrillators or cardiac valve morphological abnormalities (≥Grade 2). Subjects with grade 1 abnormalities (ie, mild regurgitation/stenosis) are eligible for enrollment. Subjects with moderate valve thickening were not eligible. Subjects with controlled atrial fibrillation for >30 days prior to dosing were eligible. (14) Patients with previous systemic anti-cancer treatment (chemotherapy, immunotherapy, biological therapy, vaccine treatment within 3 weeks before study treatment, or chemotherapy without delayed toxicity within 2 weeks before study treatment). (15) Any serious or unstable pre-existing illness, mental illness, or other condition that may affect subject safety, obtaining informed consent, or compliance with research procedures. (16) History of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subjects with laboratory evidence of cure of HBV and/or HCV will be admitted.

研究实施时间：

Study execute time：

从 From 2023-12-31 00:00:00至 To 2025-12-31 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2024-02-29 00:00:00 至 To 2024-03-31 00:00:00

干预措施：

Interventions：

组别：	由于本研究为单臂研究，故不涉及随机和设盲，亦不设立平行对照组，采用外部对照	样本量：	10
Group：	Since this study is a single-arm study, it does not involve randomization and blinding, nor does it establish a parallel control group and uses external control	Sample size：	10
干预措施：	甲磺酸达拉非尼胶囊药物干预	干预措施代码：
Intervention：	Dabrafenib mesylate capsules drug intervention	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	山东	市(区县)：	济南
Country：	China	Province：	Shandong	City：	Jinan
单位(医院)：	山东大学口腔医院	单位级别：	三甲
Institution hospital：	Stomatology Hospital of Shandong University	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	客观缓解率	指标类型：	主要指标
Outcome：	objective response rate	Type：	Primary indicator
测量时间点：	开窗减压术后及肿瘤刮治术前	测量方法：
Measure time point of outcome：	After fenestration decompression and before tumor curettage	Measure method：

指标中文名：	无复发生存期	指标类型：	次要指标
Outcome：	Recurrence-free survival	Type：	Secondary indicator
测量时间点：	在前两年内每3个月一次，此后每6个月一次	测量方法：
Measure time point of outcome：	Every 3 months for the first 2 years and every 6 months thereafter	Measure method：

指标中文名：	治疗前后肿瘤细胞类型、BRAF V600E表达情况及表达区域的空间分布的变化情况	指标类型：	次要指标
Outcome：	The changes of tumor cell types, BRAF V600E expression and the spatial distribution of expression region before and after treatment	Type：	Secondary indicator
测量时间点：	开窗减压术后至肿瘤刮治术前	测量方法：
Measure time point of outcome：	After fenestration decompression and before tumor curettage	Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	肿瘤	组织：
Sample Name：	tumor	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation after use	Note：

标本中文名：	肿瘤旁组织	组织：
Sample Name：	adjacent tumor tissue	Tissue：
人体标本去向	使用后保存	说明
Fate of sample：	Preservation after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	18	岁 years
最大 Max age	65	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：	无
Blinding：	None
试验完成后的统计结果（上传文件）：	点击下载
Calculated Results after the Study Completed(upload file)：	download

是否共享原始数据： IPD sharing	是Yes
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	采用临床试验公共管理平台ResMan，并向公众开放查询。(www.medresman.org)
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	ResMan, a clinical trial public management platform, was used and opened to the public for enquiry. (www.medresman.org)
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	本研究将采用病例报告表（CRF）辅助使用临床试验公共管理平台ResMan，进行研究数据的采集与管理。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	In this study, case report Form (CRF) will be used to assist ResMan, a public clinical trial management platform, to collect and manage research data.
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2024-02-05 16:19:07