Clinical Study of Neoadjuvant Targeted Therapy for Ameloblastoma

Launched by SHANGHAI NINTH PEOPLE'S HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIVERSITY · Oct 20, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients with a specific type of jaw tumor called ameloblastoma that has a genetic mutation known as BRAF V600E. The goal is to see if using targeted therapy with two medications, dabrafenib and trametinib, before surgery can help shrink the tumor enough to allow for a less invasive surgical option. Researchers want to find out how many patients who would normally need a larger jaw surgery can instead have a procedure that preserves more of their jaw.

To participate in this study, individuals must be between 18 and 65 years old and have been diagnosed with the solid or multicystic type of ameloblastoma that shows the BRAF V600E mutation. They should be planning to undergo surgery for their tumor and must meet certain health criteria, ensuring their body can handle the treatment. Participants can expect to receive the targeted therapy for a period before their scheduled surgery, and they will be closely monitored throughout the trial. It's important for potential participants to discuss any concerns with their healthcare provider to see if this study is a good fit for them.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Age 18-65 years;
• • 2. Diagnosed with solid/multicystic type ameloblastoma with confirmed BRAF V600E mutation by next-generation sequencing (NGS);
• • 3. Requires mandibular segmental resection at diagnosis, confirmed by two or more chief physicians;
• • 4. No distant metastasis or malignancy;
• • 5. ECOG score 0-1;
• • 6. Willing to undergo surgery after induction therapy;
• • 7. No significant contraindications to MEK and BRAF inhibitors;
• 8. Major organ function meets the following standards:
• • 1. 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);
• • 2. 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;
• • 3. Coagulation: INR or PT ≤ 1.5×ULN (anticoagulant-treated subjects must have PT within the intended range);
• • 9. 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.
• • 10. Voluntary participation with signed informed consent, good compliance, and cooperation for follow-up.
• Exclusion Criteria:
• • 1. Previous use of dabrafenib, trametinib, or other BRAF/MEK inhibitors;
• • 2. Active autoimmune diseases (stable conditions not requiring systemic immunosuppression allowed);
• • 3. 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);
• • 4. Known allergy to study drugs or their excipients, or severe allergic reactions to other monoclonal antibodies or targeted drugs;
• • 5. Myocardial infarction, severe/unstable angina, NYHA class II or higher heart failure, significant arrhythmias, or symptomatic congestive heart failure within 6 months before enrollment;
• • 6. 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);
• • 7. History of allogeneic organ or hematopoietic stem cell transplantation;
• • 8. Known history of substance abuse or drug addiction;
• • 9. Pregnant or breastfeeding women;
• • 10. 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;
• • 11. 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.