Trial Title:
Clinical Study of Neoadjuvant Targeted Therapy for Ameloblastoma
NCT ID:
NCT06653517
Condition:
Ameloblastoma
BRAF V600E Mutation Positive
Conditions: Official terms:
Ameloblastoma
Adamantinoma
Trametinib
Dabrafenib
Conditions: Keywords:
Dabrafenib
Trametinib
BRAF V600E Mutation
Conventional Ameloblastoma
Preoperative Targeted Induction Therapy
Mandibular Continuity-Preserving Surgery
Non-radical Resectable Surgery
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dabrafenib
Description:
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.
Arm group label:
Dabrafenib and Trametinib Treatment Arm
Other name:
Tafinlar
Intervention type:
Drug
Intervention name:
Trametinib
Description:
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.
Arm group label:
Dabrafenib and Trametinib Treatment Arm
Other name:
Mekinist
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.
Detailed description:
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
OUTLINE:
Dabrafenib:
Dosage: 150 mg twice daily (total daily dose of 300 mg). Administration: Must be taken in
combination with trametinib until disease progression or intolerable toxicity occurs.
Administer at least 1 hour before or 2 hours after a meal, with approximately 12 hours
between doses. Take at the same time each day. If a dose is missed and less than 6 hours
remain until the next dose, the missed dose should not be taken. When used in combination
with trametinib, take trametinib once daily at the same time as the morning or evening
dose of dabrafenib. Do not open, crush, or break the capsules.
Trametinib:
Dosage: 2 mg once daily orally, in combination with dabrafenib, until disease progression
or intolerable toxicity occurs.
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. If less than 12 hours remain until the next dose, the missed
dose should not be taken. When used in combination with dabrafenib, take trametinib once
daily at the same time as the morning or evening dose of dabrafenib. Do not chew or crush
the tablets.
Treatment Cycle:
Cycle Length: Each cycle lasts 30 days. Initial Follow-Up: Follow-up after each of the
first two cycles with a consultation, physical examination, imaging studies, and relevant
laboratory tests to evaluate drug toxicity, safety, and tumor shrinkage rate.
Adjustment and Transition to Surgery:
Toxicity Management: If intolerable drug toxicity or adverse reactions occur that cannot
be managed by dose adjustment, discontinue treatment immediately and switch to
traditional surgical treatment.
Post Two-Cycles Evaluation: After the first two cycles, if intolerable adverse reactions
persist or the tumor continues to progress despite dose adjustments, switch to
traditional surgical treatment. If the tumor does not progress, continue long-term
medication.
Long-Term Treatment Follow-Up:
Follow-Up Schedule: Conduct follow-up evaluations every two cycles, including
consultations, physical examinations, imaging studies, and relevant laboratory tests to
evaluate drug toxicity, safety, and tumor shrinkage rate.
Criteria for Surgery: If tumor shrinkage reaches a plateau or the patient meets the
criteria for mandibular preservation surgery, and the surgical plan is confirmed
independently by at least two chief physicians in the department, record this in the case
report form and discontinue the medication in preparation for scheduled surgery.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
65 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Address:
City:
Shanghai
Zip:
200011
Country:
China
Status:
Recruiting
Contact:
Last name:
HE Yue, PHD;MD
Start date:
January 1, 2023
Completion date:
December 31, 2029
Lead sponsor:
Agency:
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Agency class:
Other
Source:
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06653517
