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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2015-00169 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| ENT0043 | Other Identifier | OnCore |
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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
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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.
PRIMARY OBJECTIVES:
I. To observe the response rate of ameloblastoma to dabrafenib and trametinib at 6 weeks.
SECONDARY OBJECTIVES:
I. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabrafenib | Drug | Given PO |
|
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| Measure | Description | Time Frame |
|---|---|---|
| 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:
The outcome is reported as the number of participants achieving the different levels of tumor response per RECIST, a number without dispersion. | 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alexander Colevas | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University, School of Medicine | Stanford | California | 94305 | United States |
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| Label | URL |
|---|---|
| Stanford Cancer Institute Trials | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Dabrafenib) | Patients receive dabrafenib orally twice daily every 12 hours plus trametinib daily orally 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Dabrafenib) | Patients receive dabrafenib orally twice daily every 12 hours plus trametinib daily orally 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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:
The outcome is reported as the number of participants achieving the different levels of tumor response per RECIST, a number without dispersion. | Posted | Count of Participants | Participants | 6 weeks |
|
6 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Dabrafenib) | Patients receive dabrafenib orally twice daily every 12 hours plus trametinib daily orally 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Flu like symptoms | General disorders | CTCAE v (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. A. Dimitrios Colevas, Professor of Medicine (Oncology) | Stanford University | 650-724-9707 | colevas@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 21, 2018 | Jan 8, 2020 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D000564 | Ameloblastoma |
| D050398 | Adamantinoma |
| ID | Term |
|---|---|
| D009808 | Odontogenic Tumors |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D001859 | Bone Neoplasms |
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| ID | Term |
|---|---|
| C561627 | dabrafenib |
| C560077 | trametinib |
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| Trametinib | Drug | Given PO |
|
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| 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. | 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. | 6 weeks |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | 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. | On the basis of futility due to study closure with inadequate accrual, post-surgical research specimens were not analyzed. | Posted | 6 weeks |
|
|
| Secondary | 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. | On the basis of futility due to study closure with inadequate accrual, post-surgical research specimens were not analyzed. | Posted | 6 weeks |
|
|
| Secondary | 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. | On the basis of futility due to study closure with inadequate accrual, post-surgical research specimens were not analyzed. | Posted | 6 weeks |
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| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| Headache | Nervous system disorders | CTCAE v (4.0) | Systematic Assessment |
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| Fatigue | General disorders | CTCAE v (4.0) | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE v (4.0) | Systematic Assessment |
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| Rash acneform | Skin and subcutaneous tissue disorders | CTCAE v(4.0) | Systematic Assessment |
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| Weight loss | Investigations | CTCAE v(4.0) | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | CTCAE v(4.0) | Systematic Assessment |
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| Dermatologic syndrome | Skin and subcutaneous tissue disorders | CTCAE v (4.0) | Systematic Assessment |
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| D009371 |
| Neoplasms by Site |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |