AmeloblastomaPhase 2NCT02367859
Dabrafenib and Trametinib in Treating Patients With BRAF Mutated Ameloblastoma
A Phase 2 study testing Dabrafenib and Trametinib in people with Ameloblastoma and BRAF Gene Mutation, run by Stanford University at 1 site in United States.
Trial summary
This pilot clinical trial studies dabrafenib and trametinib in treating patients with ameloblastoma and a specific mutation (change) in the BRAF gene. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ameloblastoma, BRAF Gene Mutation
- What is being tested?
- Dabrafenib and Trametinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2017to 26 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histological diagnosis of ameloblastoma; all stages are eligible; patients must have evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E or other known dabrafenib sensitive BRAF mutation in tumor by any Clinical Laboratory Improvement Amendments (CLIA) certified lab; may include, for example, Sanger sequencing, SNaPshot platform, immunohistochemistry, Foundation One tests, etc.)
- Life expectancy > 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Absolute neutrophil count (ANC) > 1.5 x10^9/L
- Platelet (PLT) > 99 x 10^9/L
Show all 15Show fewer
- Hemoglobin > 8 g/dL
- Total bilirubin (Tbili) < 1.6 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.6 x ULN
- Alkaline phosphatase (alk phos) < 2.6 x ULN
- Serum creatinine < 1.6 x ULN or creatinine clearance > 50 ml/min
- Ability to understand and the willingness to sign a written informed consent document
- Patients of childbearing potential must agree to use effective contraception until at least 6 months after treatment with dabrafenib
- Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
- Left ventricular ejection fraction equal to or greater than normal
Who cannot join
- No prior treatment with agents targeting BRAF mutant tyrosine kinases or radiation of target lesions
- Invasive malignancy other than ameloblastoma within 3 years, excluding curatively treated basal cell carcinoma, and other highly curable cancers such as early stage cutaneous squamous cell carcinoma (T1 NO) cervical carcinoma in situ (CIS), early stage prostate cancer, thyroid cancer or breast cancer
- Uncontrolled hypertension, chronic heart failure (CHF), or other major medical illness
- Prior allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib
- Concomitant use of strong inhibitors (e.g., ketoconazole, nefazodone, clarithromycin, gemfibrozil) or strong inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St John's wort) of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8)
- Concomitant use of proton pump inhibitors, H2-receptor antagonists, antacids
Show all 13Show fewer
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Pregnant or nursing patients; women of childbearing potential must have a negative pregnancy test within 14 days of enrollment
- Electrocardiogram (EKG) with QTcB (Bazett's formula) > 480 ms done within 14 days of enrollment
- Interstitial lung disease or pneumonitis
- A history of retinal vein occlusion (RVO)
- Congestive heart failure NYHA class III or worse (Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.)
- A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Stanford, California, 94305
About this study
Official title: A Pilot Study of Dabrafenib and Trametinib for Patients With BRAF Mutated Ameloblastoma
This pilot clinical trial studies dabrafenib and trametinib in treating patients with ameloblastoma and a specific mutation (change) in the BRAF gene. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To observe the response rate of ameloblastoma to dabrafenib and trametinib at 6 weeks.
SECONDARY OBJECTIVES:
- Feasibility and safety in this patient population. II. Response will be assessed pathologically. III. Two main histologic assays for treatment response will be used: tumor necrosis and phosphorylated-mitogen-activated protein kinase kinase 1 (MEK), phosphorylated-extracellular signal-regulated kinase (ERK), and Ki-67 levels as measured by immunohistochemistry.
OUTLINE:
Patients receive dabrafenib orally (PO) twice daily (BID) every 12 hours and trametinib 2 mg daily PO for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients whose disease is judged to be not amenable to resection will continue dabrafenib and trametinib indefinitely as long as there has not been tumor progression.
After completion of study treatment, patients are followed up for at least 4 weeks.
- Conditions
- Ameloblastoma, BRAF Gene Mutation
- Being tested
- Dabrafenib, Trametinib
- Keywords
- ameloblastoma, BRAF, odontogenic cancer, adamantinoma
- Medical subject headings
- Ameloblastoma, Adamantinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DabrafenibDrug
Also called BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436, Tafinlar
Given PO
TrametinibDrug
Also called Mekinist
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (dabrafenib) | Experimental | Patients receive dabrafenib PO BID every 12 hours plus trametinib daily PO for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients whose disease is judged to be not amenable to resection will continue dabrafenib and trametinib indefinitely as long as there has not been tumor progression. Receives: Drug: Dabrafenib; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response
Tumor response was assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Overall tumor response was assessed as the number of participants achieving either a complete response (CR) or a partial response (PR). The criteria are:
- CR = Disappearance of all target lesions
- PR = ≥ 30% decrease in the sum of the longest diameter of target lesions
- Overall Response (OR) = CR + PR
- Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)
- Stable disease (SD) = Small changes that do not meet any of the above criteria
The outcome is reported as the number of participants achieving the different levels of tumor response per RECIST, a number without dispersion.
Measured: 6 weeks
Secondary outcomes (3)
Percent Tumor Necrosis
Percent of tumor necrosis at the time of endpoint biopsy or surgical resection will be assessed. The tumor specimen from resection will be examined and the volume of the necrosis compared to the volume of the total tumor determined by central pathology. Percent tumor necrosis, in increments of 10%, will be determined. The outcome will be reported as the mean percent tumor necrosis, with standard deviation.
Measured: 6 weeks
Change in Proliferation
An immunohistochemical laboratory analysis to assess proliferation will be performed on the initial pre-treatment biopsy (baseline) vs either the endpoint tumor biopsy or the tumor specimen from the resection. Ki-67 immunohistochemistry will be scored by at least 2 pathologists using percentage positive cells as the primary metric. Proliferation will be assessed as the difference from baseline in Ki-67 labeling to the end of treatment (tumor biopsy or the tumor specimen). The outcome will be expressed as the mean, with standard deviation.
Measured: 6 weeks
Phosphorylation of Tumor Markers MEK and ERK
An immunohistochemical laboratory analysis to assess phosphorylation of the tumor markers MEK and ERK on the initial pre-treatment biopsy (baseline) vs either the endpoint tumor biopsy or the tumor specimen from the resection. Immunohistochemistry will be scored by at least 2 pathologists using percentage positive cells and intensity of staining as the primary metrics. Phosphorylation of MEK and ERK will be assessed as the observed difference in phosphorylated MEK and ERK labeling from baseline to the end of treatment (tumor biopsy or the tumor specimen). The outcome will be expressed as the mean, with standard deviation.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2015 (estimated)
- Study start17 Jul 2017
- Primary completion5 Nov 2018
- Study completion26 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AmeloblastomaStudies of the same condition, open and under way.
- More trials run by Stanford 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
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Principal investigator, A. Dimitrios Colevas, Stanford University
- Investigators
- Alexander Colevas, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02367859
- Sponsor's protocol ID
- IRB-32275
- Other IDs
- NCI-2015-00169, ENT0043
- Status last verified
- Jan 2024
- First submitted
- 13 Feb 2015
- Last updated
- 30 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Dabrafenib and Trametinib for Patients With BRAF Mutated Ameloblastoma
- ClinicalTrials.gov ID
- NCT02367859
- Acronym / sponsor ID
- IRB-32275
- Conditions
- Ameloblastoma, BRAF Gene Mutation
- Keywords
- ameloblastoma, BRAF, odontogenic cancer, adamantinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 17 Jul 2017 (actual)
- Primary completion
- 5 Nov 2018 (actual)
- Study completion
- 26 Jun 2019 (actual)
- First posted
- 20 Feb 2015 (estimated)
- Results
- Posted 21 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This pilot clinical trial studies dabrafenib and trametinib in treating patients with ameloblastoma and a specific mutation (change) in the BRAF gene. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To observe the response rate of ameloblastoma to dabrafenib and trametinib at 6 weeks.
SECONDARY OBJECTIVES:
- Feasibility and safety in this patient population. II. Response will be assessed pathologically. III. Two main histologic assays for treatment response will be used: tumor necrosis and phosphorylated-mitogen-activated protein kinase kinase 1 (MEK), phosphorylated-extracellular signal-regulated kinase (ERK), and Ki-67 levels as measured by immunohistochemistry.
OUTLINE:
Patients receive dabrafenib orally (PO) twice daily (BID) every 12 hours and trametinib 2 mg daily PO for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients whose disease is judged to be not amenable to resection will continue dabrafenib and trametinib indefinitely as long as there has not been tumor progression.
After completion of study treatment, patients are followed up for at least 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (dabrafenib) | Experimental | Drug: Dabrafenib, Drug: TrametinibPatients receive dabrafenib PO BID every 12 hours plus trametinib daily PO for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients whose disease is judged to be not amenable to resection will continue dabrafenib and trametinib indefinitely as long as there has not been tumor progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histological diagnosis of ameloblastoma; all stages are eligible; patients must have evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E or other known dabrafenib sensitive BRAF mutation in tumor by any Clinical Laboratory Improvement Amendments (CLIA) certified lab; may include, for example, Sanger sequencing, SNaPshot platform, immunohistochemistry, Foundation One tests, etc.)
- Life expectancy > 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Absolute neutrophil count (ANC) > 1.5 x10^9/L
Key exclusion criteria (13 listed)
- No prior treatment with agents targeting BRAF mutant tyrosine kinases or radiation of target lesions
- Invasive malignancy other than ameloblastoma within 3 years, excluding curatively treated basal cell carcinoma, and other highly curable cancers such as early stage cutaneous squamous cell carcinoma (T1 NO) cervical carcinoma in situ (CIS), early stage prostate cancer, thyroid cancer or breast cancer
- Uncontrolled hypertension, chronic heart failure (CHF), or other major medical illness
- Prior allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib
- Concomitant use of strong inhibitors (e.g., ketoconazole, nefazodone, clarithromycin, gemfibrozil) or strong inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St John's wort) of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8)
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: BRAF Inhibitor GSK2118436, GSK-2118436A, GSK2118436, TafinlarGiven PO | Drug | Treatment (dabrafenib) |
| TrametinibAlso: MekinistGiven PO | Drug | Treatment (dabrafenib) |
Primary outcome
Tumor Response
Time frame: 6 weeks
Tumor response was assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Overall tumor response was assessed as the number of participants achieving either a complete response (CR) or a partial response (PR). The criteria are: * CR = Disappearance of all target lesions * PR = ≥ 30% decrease in the sum of the longest diameter of target lesions * Overall Response (OR) = CR + PR * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s) * Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome is reported as the number of participants achieving the different levels of tumor response per RECIST, a number without dispersion.
3 secondary outcomes
Percent Tumor Necrosis
Time frame: 6 weeks
Change in Proliferation
Time frame: 6 weeks
Phosphorylation of Tumor Markers MEK and ERK
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Stanford Cancer Institute TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Ameloblastoma
Recruiting
Virtual Lesion Segmentation and Mandibular Ameloblastoma Radiographic Safety Margin
Ameloblastoma
Not yet recruitingPhase 2/3
Neoadjuvant Therapy With Conservative Surgery vs. Up-front Conservative Surgery for BRAF V600E-Mutated Ameloblastoma
Ameloblastoma
RecruitingPhase 2
Clinical Study of Neoadjuvant Targeted Therapy for Ameloblastoma
Ameloblastoma, BRAF V600E Mutation Positive
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. This study is not recruiting at the moment.
Alexander Colevas principal investigator
Stanford University
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 Gene Mutation, run by Stanford University at 1 site in United States.
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 15 inclusion and 13 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: finished, as of the sponsor's last update on 30 Jan 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 United States. 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?
Yes. Results are posted in the registry (first posted 21 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumor Response (time frame: 6 weeks). 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 30 Jan 2024.