Neoadjuvant targeted therapy for ameloblastoma

Neoadjuvant BRAFV600E-Targeted Therapy for Conventional Ameloblastoma of the Jaw:A Single-Arm Clinical Study

This study is testing if a new targeted therapy can help patients with a specific type of jaw tumor called ameloblastoma have less invasive surgery instead of more extensive surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University (Academic / other)
• Drugs / interventions: trametinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06653517 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the effectiveness of preoperative targeted therapy using dabrafenib and trametinib in patients with conventional ameloblastoma that have the BRAF V600E mutation. The primary objectives are to determine the proportion of patients who can undergo mandibular preservation surgery instead of segmental resection after treatment, and to assess the resectability of initially non-radically resectable cases. Secondary objectives include evaluating radiological and pathological responses, local recurrence-free survival, and the safety and feasibility of the treatment in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 diagnosed with solid or multicystic ameloblastoma harboring the BRAF V600E mutation who require mandibular segmental resection.

Not a fit: Patients with distant metastasis, other malignancies, or significant contraindications to MEK and BRAF inhibitors may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve surgical outcomes and quality of life for patients with ameloblastoma.

How similar studies have performed: While targeted therapies have shown promise in other cancers, this specific approach for ameloblastoma is novel and has not been extensively tested.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: CAO Wei, PHD;MD — Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
• Study coordinator: ZHAO Zhang

Conditions Ameloblastoma; BRAF V600E Mutation Positive; Dabrafenib; Trametinib; BRAF V600E Mutation; Conventional Ameloblastoma; Preoperative Targeted Induction Therapy; Mandibular Continuity-Preserving Surgery