Clinical Study of Neoadjuvant Targeted Therapy for Ameloblastoma

NCT06653517 | Recruiting Phase 2 DMC

• 1 other identifier: NETCAM_2024CT
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ameloblastoma; BRAF V600E Mutation Positive

Keywords

Dabrafenib; Trametinib; BRAF V600E Mutation; Conventional Ameloblastoma; Preoperative Targeted Induction Therapy; Mandibular Continuity-Preserving Surgery; Non-radical Resectable Surgery

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients Eligible for Mandibular Continuity-Preserving Surgery

  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.

  After completion of two 30-day cycles of therapy (approximately 2 months)

• Proportion of Non-radical Resectable Cases Becoming Resectable

  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.

  After completion of two 30-day cycles of therapy (approximately 2 months)

Secondary Outcomes (4)

• 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

Study Arms (1)

Dabrafenib and Trametinib Treatment Arm

EXPERIMENTAL

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.

Drug: Dabrafenib; Drug: Trametinib

Interventions

Dabrafenib DRUG

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.

Also known as: Tafinlar

Dabrafenib and Trametinib Treatment Arm

Trametinib DRUG

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.

Also known as: Mekinist

Dabrafenib and Trametinib Treatment Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University: lead

Study Sites (1)

Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200011, China

RECRUITING

MeSH Terms

Conditions

Ameloblastoma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Odontogenic Tumors; Neoplasms by Histologic Type; Neoplasms

Study Officials

• CAO Wei, PHD;MD

  Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ZHAO Zhang

CONTACT

+86 15150104115; zaidezaidezz@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 22, 2024
• Study Start: January 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029
• Last Updated: October 22, 2024

Record last verified: 2024-10

Locations

CN (1)