AmeloblastomaPhase 2/3NETCAM-RCTNCT06819605
Neoadjuvant Therapy With Conservative Surgery vs. Up-front Conservative Surgery for BRAF V600E-Mutated Ameloblastoma
A Phase 2/3 study testing Dabrafenib and trametinib (combination) in people with Ameloblastoma, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University.
Trial summary
Ameloblastoma is the most common benign odontogenic tumor, characterized by high local invasiveness and a high recurrence rate. Currently, surgical treatment is the standard treatment modality. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Ameloblastoma
- What is being tested?
- Dabrafenib and trametinib (combination)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2025to 31 Dec 2028
- Phase
- Phase 2/3
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 12 years.
- Pathologically confirmed diagnosis of solid or cystic ameloblastic tumors, or recurrent unicystic ameloblastic tumors.
- Presence of BRAF V600E mutation confirmed by next-generation sequencing (NGS) in tumor tissue.
- Requires mandible resection at initial diagnosis (limited to segmental mandibulectomy, subtotal maxillectomy, or total maxillectomy).
- No distant metastasis or malignancy.
- ECOG performance status of 0-1.
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- Willing to undergo surgical treatment after neoadjuvant therapy.
- No significant contraindications to MEK inhibitors or BRAF inhibitors.
- Adequate organ function as defined by the following standards: a) Hematologic criteria: WBC ≥ 4.0 × 10^9/L, ANC ≥ 1.5 × 10^9/L, PLT ≥ 100 × 10^9/L, Hb ≥ 90 g/L (no blood transfusion or blood products within the past 14 days, no G-CSF or other hematopoietic growth factors used to correct). b) Biochemical criteria: Serum albumin ≥ 3.0 g/dL (30 g/L), TBIL ≤ 1.5 × ULN, ALT, AST ≤ 2.5 × ULN, BUN and CRE ≤ 1.5 × ULN or estimated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula). c) Normal coagulation function: Defined as INR or PT ≤ 1.5 × ULN; for patients on anticoagulant therapy, PT within the therapeutic range for the anticoagulant drug.
- Women of childbearing potential must have used reliable contraception, undergone a pregnancy test within 7 days prior to enrollment with a negative result, and be willing to continue using effective contraception during the study and for 16 weeks after the last dose of Trametinib combined with Dabrafenib. Male participants with female partners of childbearing potential should use effective contraception during the study and for 16 weeks after the last dose of Trametinib combined with Dabrafenib.
Who cannot join
- Previous treatment with Dabrafenib, Trametinib, or any other BRAF inhibitors or MEK inhibitors.
- Presence of active autoimmune disease. Subjects with stable autoimmune conditions not requiring systemic immunosuppressive therapy are allowed, such as: type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia).
- Congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10^4 copies/ml), or hepatitis C (positive HCV antibodies with HCV RNA above the detection threshold of the testing method).
- Known allergy to the study drugs or any of their excipients; or a history of severe allergic reaction to other monoclonal antibodies or targeted therapies.
- History of myocardial infarction, severe/uncontrolled angina, NYHA class ≥2 heart failure, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure within 6 months prior to enrollment.
- Receipt of a live vaccine within 4 weeks prior to first dose of study drug. Seasonal influenza vaccines are allowed if inactivated and injected, but live attenuated influenza vaccines (e.g., nasal spray) are not allowed.
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- Known history of organ transplantation or hematopoietic stem cell transplantation.
- Known history of substance abuse or drug addiction.
- Pregnant or breastfeeding women.
- Diagnosis of any other malignancy within 5 years prior to study entry, except for cured localized skin basal cell carcinoma, squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, and benign tumors.
- Presence of other serious physical or mental health conditions, or laboratory abnormalities that may increase the risk of participating in the study or interfere with the study results, as determined by the investigator.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Neoadjuvant Therapy With Dabrafenib and Trametinib Followed by Curettage/Fenestration Surgery Versus Up-front Curettage and Fenestration Surgery in BRAF V600E Mutated Ameloblastoma: A Randomized Controlled Clinical Trial
Ameloblastoma is the most common benign odontogenic tumor, characterized by high local invasiveness and a high recurrence rate. Currently, surgical treatment is the standard treatment modality. The main surgical approaches include radical resection represented by local extended resection (with a safety margin of more than 2 cm) and conservative procedures represented by curettage and fenestration. Although radical resection can effectively treat the disease, it often leads to severe jaw bone defects and even disrupts the continuity of the jaw bone. However, the conservative procedures have a recurrence rate of approximately 40%.
This study aims to reduce the recurrence rate of conservative procedures by using neoadjuvant therapy with dabrafenib combined with trametinib, and to reduce surgical trauma while improving the radical cure effect. The endpoints of this study are the 3-year and 5-year recurrence rates, as well as the effectiveness and safety of the neoadjuvant therapy.
Read the detailed description
The primary endpoints are the 3-year and 5-year recurrence - free survival rates after neoadjuvant therapy followed by curettage and fenestration surgery. The secondary endpoints are the radiological response, pathological response, and safety of the neoadjuvant therapy with dabrafenib combined with trametinib.
- Conditions
- Ameloblastoma
- Being tested
- Dabrafenib and trametinib (combination)
- Keywords
- Ameloblastoma, Neoadjuvant therapy, Curettage and fenestration surgery, Recurrence - free survival rate, BRAF V600E
- Medical subject headings
- Ameloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dabrafenib and trametinib (combination)Drug
This clinical study investigates the combination of Dabrafenib (2 mg once daily for adults; 0.025 mg/kg/day for children ≥12 years, orally once daily) and Trametinib (2 mg once daily for adults; 0.025 mg/kg/day for children ≥12 years, orally once daily) as a treatment for [specific condition]. The treatment will be administered until disease progression or intolerable toxicities occur. Both medications should be taken at least 1 hour before or 2 hours after a meal, at the same time each day. If a dose is missed, it should be taken within 12 hours of the scheduled time. If less than 12 hours remain before the next dose, the missed dose should not be taken. Both medications should be taken in combination with the scheduled dose of Dabrafenib at either morning or evening and must not be chewed or crushed.
Each treatment cycle lasts 30 days. At the end of each cycle, follow-up assessments will include clinical examination, laboratory tests to evaluate drug safety, and imaging studies to a
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | Curettage and fenestration surgery alone |
| Neoadjuvant group | Experimental | Neoadjuvant therapy chemotherapy before curettage and fenestration surgery Receives: Drug: Dabrafenib and trametinib (combination) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence - free survival rates
To evaluate the recurrence-free survival after neoadjuvant therapy with dabrafenib and trametinib, followed by curettage and fenestration surgery.
Measured: Up to 5 years
Secondary outcomes (3)
Radiological response
The radiological response to neoadjuvant therapy with Dabrafenib and Trametinib in patients with ameloblastoma will be assessed through three-dimensional volumetric imaging (e.g., CT scans with 3D reconstruction) at predefined intervals. Tumor volume changes, as determined by 3D reconstruction, will be used to evaluate the radiological response.
Measured: 3 months
Pathological response
The pathological response to neoadjuvant therapy with Dabrafenib and Trametinib in patients with ameloblastoma will be assessed through post-treatment surgical specimens.
Measured: 4 months
AEs will be recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
The safety of neoadjuvant therapy with Dabrafenib and Trametinib in patients with ameloblastoma will be assessed through monitoring adverse events (AEs). AEs will be recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and graded based on severity (Grade 1 to Grade 5) and their relationship to the study drugs.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2025
- Study start1 Mar 2025 (estimated)
- Primary completion30 Oct 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AmeloblastomaStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06819605
- Sponsor's protocol ID
- NETCAM_2025CT
- Other IDs
- SH9H-2024-T470-1
- Acronym
- NETCAM-RCT
- Status last verified
- Feb 2025
- First submitted
- 6 Feb 2025
- Last updated
- 11 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Grynberg S, Vered M, Shapira-Frommer R, Asher N, Ben-Betzalel G, Stoff R, Steinberg Y, Amariglio N, Greenberg G, Barshack I, Toren A, Yahalom R, Schachter J, Rechavi G, Hirschhorn A, Abebe Campino G. Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach. J Natl Cancer Inst. 2024 Apr 5;116(4):539-546. doi: 10.1093/jnci/djad232.
PubMed 37966914Gasparro R, Giordano F, Campana MD, Aliberti A, Landolfo E, Dolce P, Sammartino G, di Lauro AE. The Effect of Conservative vs. Radical Treatment of Ameloblastoma on Recurrence Rate and Quality of Life: An Umbrella Review. J Clin Med. 2024 Sep 9;13(17):5339. doi: 10.3390/jcm13175339.
PubMed 39274556
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Therapy With Dabrafenib and Trametinib Followed by Curettage/Fenestration Surgery Versus Up-front Curettage and Fenestration Surgery in BRAF V600E Mutated Ameloblastoma: A Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT06819605
- Acronym / sponsor ID
- NETCAM-RCT / NETCAM_2025CT
- Conditions
- Ameloblastoma
- Keywords
- Ameloblastoma, Neoadjuvant therapy, Curettage and fenestration surgery, Recurrence - free survival rate, BRAF V600E
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityUniversity, hospital or other
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- 30 Oct 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 11 Feb 2025 (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.
Ameloblastoma is the most common benign odontogenic tumor, characterized by high local invasiveness and a high recurrence rate. Currently, surgical treatment is the standard treatment modality. The main surgical approaches include radical resection represented by local extended resection (with a safety margin of more than 2 cm) and conservative procedures represented by curettage and fenestration. Although radical resection can effectively treat the disease, it often leads to severe jaw bone defects and even disrupts the continuity of the jaw bone. However, the conservative procedures have a recurrence rate of approximately 40%.
This study aims to reduce the recurrence rate of conservative procedures by using neoadjuvant therapy with dabrafenib combined with trametinib, and to reduce surgical trauma while improving the radical cure effect. The endpoints of this study are the 3-year and 5-year recurrence rates, as well as the effectiveness and safety of the neoadjuvant therapy.
Detailed description
The primary endpoints are the 3-year and 5-year recurrence - free survival rates after neoadjuvant therapy followed by curettage and fenestration surgery. The secondary endpoints are the radiological response, pathological response, and safety of the neoadjuvant therapy with dabrafenib combined with trametinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –Curettage and fenestration surgery alone |
| Neoadjuvant group | Experimental | Drug: Dabrafenib and trametinib (combination)Neoadjuvant therapy chemotherapy before curettage and fenestration surgery |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 12 years.
- Pathologically confirmed diagnosis of solid or cystic ameloblastic tumors, or recurrent unicystic ameloblastic tumors.
- Presence of BRAF V600E mutation confirmed by next-generation sequencing (NGS) in tumor tissue.
- Requires mandible resection at initial diagnosis (limited to segmental mandibulectomy, subtotal maxillectomy, or total maxillectomy).
- No distant metastasis or malignancy.
Key exclusion criteria (11 listed)
- Previous treatment with Dabrafenib, Trametinib, or any other BRAF inhibitors or MEK inhibitors.
- Presence of active autoimmune disease. Subjects with stable autoimmune conditions not requiring systemic immunosuppressive therapy are allowed, such as: type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia).
- Congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10^4 copies/ml), or hepatitis C (positive HCV antibodies with HCV RNA above the detection threshold of the testing method).
- Known allergy to the study drugs or any of their excipients; or a history of severe allergic reaction to other monoclonal antibodies or targeted therapies.
- History of myocardial infarction, severe/uncontrolled angina, NYHA class ≥2 heart failure, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure within 6 months prior to 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 |
|---|---|---|
| Dabrafenib and trametinib (combination)This clinical study investigates the combination of Dabrafenib (2 mg once daily for adults; 0.025 mg/kg/day for children ≥12 years, orally once daily) and Trametinib (2 mg once daily for adults; 0.025 mg/kg/day for children ≥12 years, orally once daily) as a treatment for [specific condition]. The treatment will be administered until disease progression or intolerable toxicities occur. Both medications should be taken at least 1 hour before or 2 hours after a meal, at the same time each day. If a dose is missed, it should be taken within 12 hours of the scheduled time. If less than 12 hours remain before the next dose, the missed dose should not be taken. Both medications should be taken in combination with the scheduled dose of Dabrafenib at either morning or evening and must not be chewed or crushed. Each treatment cycle lasts 30 days. At the end of each cycle, follow-up assessments will include clinical examination, laboratory tests to evaluate drug safety, and imaging studies to a | Drug | Neoadjuvant group |
Primary outcome
Recurrence - free survival rates
Time frame: Up to 5 years
To evaluate the recurrence-free survival after neoadjuvant therapy with dabrafenib and trametinib, followed by curettage and fenestration surgery.
3 secondary outcomes
Radiological response
Time frame: 3 months
Pathological response
Time frame: 4 months
AEs will be recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time frame: 1 year
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 11 Feb 2025.
- Results publication: PubMed 37966914Grynberg S, Vered M, Shapira-Frommer R, Asher N, Ben-Betzalel G, Stoff R, Steinberg Y, Amariglio N, Greenberg G, Barshack I, Toren A, Yahalom R, Schachter J, Rechavi G, Hirschhorn A, Abebe Campino G. Neoadjuvant BRAF-targeted therapy for ameloblastoma of the mandible: an organ preservation approach. J Natl Cancer Inst. 2024 Apr 5;116(4):539-546. doi: 10.1093/jnci/djad232.
- Results publication: PubMed 39274556Gasparro R, Giordano F, Campana MD, Aliberti A, Landolfo E, Dolce P, Sammartino G, di Lauro AE. The Effect of Conservative vs. Radical Treatment of Ameloblastoma on Recurrence Rate and Quality of Life: An Umbrella Review. J Clin Med. 2024 Sep 9;13(17):5339. doi: 10.3390/jcm13175339.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dabrafenib and trametinib (combination) in people with Ameloblastoma, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University.
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 10 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: opening soon, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Wei Cao, M.D., Ph.D. (+86-21-23271699-5211, caowei561521@shsmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence - free survival rates (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06819605, which also lists 2 linked publications.
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 11 Feb 2025.