Neoadjuvant BRAFV600E-Targeted Therapy for Conventional Ameloblastoma of the Jaw:A Single-Arm Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Proportion of Patients Eligible for Mandibular Continuity-Preserving Surgery
研究概览
简要总结
This study aims to evaluate the tumor shrinkage effect of preoperative targeted induction therapy with dabrafenib and trametinib in patients with conventional ameloblastoma harboring the BRAF V600E mutation. The study will assess the proportion of cases where mandibular continuity cannot be preserved that can be converted to cases where mandibular continuity is preserved, as well as the proportion of cases where complete resection is initially not feasible that become resectable.
详细描述
PRIMARY OBJECTIVES:
Ⅰ. To observe the proportion of patients with ameloblastoma requiring mandibular segmental resection at initial diagnosis who can convert to mandibular preservation surgery after preoperative induction therapy with dabrafenib and trametinib.
Ⅱ.To observe the proportion of cases initially deemed non-radical resectable Surgery that become resectable
SECONDARY OBJECTIVES:
Ⅰ. Radiological response Ⅱ. Pathological response Ⅲ. Local recurrence-free survival(LRFS) Ⅳ.Feasibility and safety in this patient population
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years;
- •Diagnosed with solid/multicystic type ameloblastoma with confirmed BRAF V600E mutation by next-generation sequencing (NGS);
- •Requires mandibular segmental resection at diagnosis, confirmed by two or more chief physicians;
- •No distant metastasis or malignancy;
- •ECOG score 0-1;
- •Willing to undergo surgery after induction therapy;
- •No significant contraindications to MEK and BRAF inhibitors;
- •Major organ function meets the following standards:
- •Hematological: WBC ≥ 4.0×10^9/L, ANC ≥ 1.5×10^9/L, PLT ≥ 100×10^9/L, Hb ≥ 90g/L (no transfusion or blood products, no use of G-CSF or other hematopoietic stimulants within 14 days);
- •Biochemical: Serum albumin ≥ 3.0 g/dL, TBIL ≤ 1.5×ULN, ALT/AST ≤ 2.5×ULN, BUN/CRE ≤ 1.5×ULN or creatinine clearance rate ≥ 60 ml/min;
- •Coagulation: INR or PT ≤ 1.5×ULN (anticoagulant-treated subjects must have PT within the intended range);
- •Women of childbearing age must use effective contraception, have a negative pregnancy test within 7 days before enrollment, and agree to use effective contraception during the study and for 16 weeks after the last dose of trametinib and dabrafenib. Male subjects with partners of childbearing age must use effective contraception during the study and for 16 weeks after the last dose of trametinib and dabrafenib.
- •Voluntary participation with signed informed consent, good compliance, and cooperation for follow-up.
排除标准
- •Previous use of dabrafenib, trametinib, or other BRAF/MEK inhibitors;
- •Active autoimmune diseases (stable conditions not requiring systemic immunosuppression allowed);
- •Congenital or acquired immunodeficiency (e.g., HIV), active hepatitis B (HBV-DNA ≥ 10^4 copies/ml), or hepatitis C (positive HCV antibody and HCR-RNA above the detection limit);
- •Known allergy to study drugs or their excipients, or severe allergic reactions to other monoclonal antibodies or targeted drugs;
- •Myocardial infarction, severe/unstable angina, NYHA class II or higher heart failure, significant arrhythmias, or symptomatic congestive heart failure within 6 months before enrollment;
- •Live vaccination within 4 weeks before the first dose of study drugs (inactivated virus vaccines allowed for seasonal flu, but live attenuated intranasal vaccines not allowed);
- •History of allogeneic organ or hematopoietic stem cell transplantation;
- •Known history of substance abuse or drug addiction;
- •Pregnant or breastfeeding women;
- •Diagnosed with any other tumors within 5 years before the study, except for locally treatable and cured basal cell carcinoma, squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ, papillary thyroid carcinoma, and benign tumors;
- •Other severe physical or mental diseases or laboratory abnormalities that may increase the risk of participation or interfere with study results, deemed unsuitable for participation by the investigator.
研究组 & 干预措施
Dabrafenib and Trametinib Treatment Arm
Dabrafenib: 150 mg twice daily, not to be taken if less than 6 hours remain to the next dose.
Trametinib: 2 mg once daily, not to be taken if less than 12 hours remain to the next dose.
Cycle Length: 30 days. Initial Follow-Up: After each of the first two cycles. Toxicity Management: Discontinue if intolerable toxicity occurs. Long-Term Follow-Up: Every two cycles. Criteria for Surgery: Confirmed by at least two chief physicians.
干预措施: Dabrafenib (Drug)
Dabrafenib and Trametinib Treatment Arm
Dabrafenib: 150 mg twice daily, not to be taken if less than 6 hours remain to the next dose.
Trametinib: 2 mg once daily, not to be taken if less than 12 hours remain to the next dose.
Cycle Length: 30 days. Initial Follow-Up: After each of the first two cycles. Toxicity Management: Discontinue if intolerable toxicity occurs. Long-Term Follow-Up: Every two cycles. Criteria for Surgery: Confirmed by at least two chief physicians.
干预措施: Trametinib (Drug)
结局指标
主要结局
Proportion of Patients Eligible for Mandibular Continuity-Preserving Surgery
时间窗: After completion of two 30-day cycles of therapy (approximately 2 months)
The proportion of patients initially requiring mandibular segmental resection who become eligible for mandibular continuity-preserving surgery after preoperative targeted induction therapy with dabrafenib and trametinib.
Proportion of Non-radical Resectable Cases Becoming Resectable
时间窗: After completion of two 30-day cycles of therapy (approximately 2 months)
The proportion of patients initially deemed non-radical resectable who become resectable after completing two cycles of preoperative targeted induction therapy with dabrafenib and trametinib.
次要结局
- Radiological Response(After completion of two 30-day cycles of therapy (approximately 2 months))
- Pathological Response(After completion of two 30-day cycles of therapy (approximately 2 months))
- Local Recurrence-Free Survival (LRFS)(3 months)
- Adverse Effects and Safety(Throughout the study period, up to 12 months)