AmeloblastomaPhase 2NETCAMNCT06653517
Clinical Study of Neoadjuvant Targeted Therapy for Ameloblastoma
A Phase 2 study testing Dabrafenib and Trametinib in people with Ameloblastoma and BRAF V600E Mutation Positive, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Ameloblastoma, BRAF V600E Mutation Positive
- What is being tested?
- Dabrafenib and Trametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2023to 31 Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200011
HE Yue, PHD;MD
About this study
Official title: Neoadjuvant BRAFV600E-Targeted Therapy for Conventional Ameloblastoma of the Jaw:A Single-Arm Clinical Study
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.
Read the 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.
- Conditions
- Ameloblastoma, BRAF V600E Mutation Positive
- Being tested
- Dabrafenib, Trametinib
- Keywords
- Dabrafenib, Trametinib, BRAF V600E Mutation, Conventional Ameloblastoma, Preoperative Targeted Induction Therapy, Mandibular Continuity-Preserving Surgery, Non-radical Resectable Surgery
- Medical subject headings
- Ameloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DabrafenibDrug
Also called Tafinlar
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.
TrametinibDrug
Also called Mekinist
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Dabrafenib; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: After completion of two 30-day cycles of therapy (approximately 2 months)
Secondary outcomes (4)
Radiological Response
The evaluation of tumor response using radiological studies such as MRI or CT scans after preoperative targeted induction therapy with dabrafenib and trametinib.
Measured: After completion of two 30-day cycles of therapy (approximately 2 months)
Pathological Response
The assessment of tumor pathological changes after preoperative targeted induction therapy with dabrafenib and trametinib, based on biopsy or surgical specimens.
Measured: After completion of two 30-day cycles of therapy (approximately 2 months)
Local Recurrence-Free Survival (LRFS)
The time from the start of treatment to the occurrence of local recurrence or death from any cause, whichever occurs first.
Measured: 3 months
Adverse Effects and Safety
The incidence and severity of adverse effects related to the combination therapy with dabrafenib and trametinib, assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: Throughout the study period, up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2024
- Study start1 Jan 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AmeloblastomaStudies of the same condition, open and under way.
- More trials run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Group Assignment
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- CAO Wei, PHD;MD, Principal investigator, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06653517
- Sponsor's protocol ID
- NETCAM_2024CT
- Acronym
- NETCAM
- Status last verified
- Oct 2024
- First submitted
- 15 Oct 2024
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant BRAFV600E-Targeted Therapy for Conventional Ameloblastoma of the Jaw:A Single-Arm Clinical Study
- ClinicalTrials.gov ID
- NCT06653517
- Acronym / sponsor ID
- NETCAM / NETCAM_2024CT
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 22 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Group Assignment
| Arm | Type | Receives |
|---|---|---|
| Dabrafenib and Trametinib Treatment Arm | Experimental | Drug: Dabrafenib, Drug: TrametinibDabrafenib: 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DabrafenibAlso: TafinlarDosage: 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. | Drug | Dabrafenib and Trametinib Treatment Arm |
| TrametinibAlso: MekinistDosage: 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. | Drug | Dabrafenib and Trametinib Treatment Arm |
Primary outcome
Proportion of Patients Eligible for Mandibular Continuity-Preserving Surgery
Time frame: After completion of two 30-day cycles of therapy (approximately 2 months)
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.
Proportion of Non-radical Resectable Cases Becoming Resectable
Time frame: After completion of two 30-day cycles of therapy (approximately 2 months)
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.
4 secondary outcomes
Radiological Response
Time frame: After completion of two 30-day cycles of therapy (approximately 2 months)
Pathological Response
Time frame: After completion of two 30-day cycles of therapy (approximately 2 months)
Local Recurrence-Free Survival (LRFS)
Time frame: 3 months
Adverse Effects and Safety
Time frame: Throughout the study period, up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
CAO Wei, PHD;MD principal investigator
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dabrafenib and Trametinib in people with Ameloblastoma and BRAF V600E Mutation Positive, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ZHAO Zhang (+86 15150104115, zaidezaidezz@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients Eligible for Mandibular Continuity-Preserving Surgery (time frame: After completion of two 30-day cycles of therapy (approximately 2 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2024.