Clinical Study of Neoadjuvant Targeted Therapy for Ameloblastoma
Neoadjuvant BRAFV600E-Targeted Therapy for Conventional Ameloblastoma of the Jaw:A Single-Arm Clinical Study
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
12 participants
Jan 1, 2023
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria13
- 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.
Exclusion Criteria11
- 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.
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Interventions
Dosage: 150 mg orally, twice daily (total daily dose of 300 mg) Administration: Administer at approximately 12 hours apart. Take at the same time each day. If a dose is missed and less than 6 hours remain until the next dose, skip the missed dose. Do not open, crush, or break the capsules. Usage in Combination: When used in combination with trametinib, trametinib should be taken once daily at the same time as either the morning or evening dose of dabrafenib to ensure synchronization of the treatment schedule.
Dosage: 2 mg orally, once daily Administration: Administer at least 1 hour before or 2 hours after a meal. Take at the same time each day. If a dose is missed, it should be taken no later than 12 hours before the next scheduled dose; otherwise, skip the missed dose. Usage in Combination: When used in combination with trametinib, trametinib should be taken once daily at the same time as either the morning or evening dose of dabrafenib to ensure synchronization of the treatment schedule.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06653517