SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02367859

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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.

NCT02367859 Ameloblastoma BRAF Gene Mutation
MeSH: Ameloblastoma Adamantinoma

3 Interventions

Name: Dabrafenib

Description: Given PO

Type: Drug

Treatment (dabrafenib)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Treatment (dabrafenib)

Name: Trametinib

Description: Given PO

Type: Drug

Treatment (dabrafenib)


Primary Outcomes

Description: RECIST v1.1 response rate

Measure: Response rate according to RECIST version (v)1.1

Time: 6 weeks

Secondary Outcomes

Description: Routine Hematoxylin and Eosin slide review will measure extent of tumor necrosis. Percentage of tumor necrosis by volume assessed. The biopsy slide of the resection specimen examined and the volume of the necrosis compared to the volume of the total tumor determined by the centrally reviewing pathologists and percentage readouts of tumor necrosis, in increments of 10%, will be determined. In addition to measuring tumor necrosis the slide review will estimate therapy effect on intact cells by estimating the percent cells with therapy-associated nuclear atypia.

Measure: Percent tumor necrosis

Time: At the time of endpoint biopsy or surgical resection

Description: Proliferation index evaluation will be performed in the laboratory on the initial pre-treatment biopsy and either the endpoint biopsy or the resection specimen. Ki-67 immunohistochemistry will be scored by at least two pathologists using percentage positive cells as the primary metric. The results of the immunohistochemical analysis will be expressed as both raw data in addition to a ratio between pre- and post- treatment.

Measure: Change in percent proliferation index by Ki67 immunohistochemistry

Time: Baseline to time of endpoint biopsy or surgical resection

Description: Immunohistochemistry evaluation for MEK/ERK will be performed on the initial pre-treatment biopsy and either the endpoint biopsy or the resection specimen. Immunohistochemistry will be scored by at least two pathologists using percentage positive cells and intensity of staining as the primary metrics. The results of the immunohistochemical analysis will be expressed as both raw data in addition to a ratio between pre- and post- treatment.

Measure: Change in expression of phosphorylation of MEK and ERK by immunohistochemistry

Time: Baseline to time of endpoint biopsy or surgical resection

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

The results of the immunohistochemical analysis will be expressed as both raw data in addition to a ratio between pre- and post- treatment.. Inclusion Criteria: - 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 - 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 Exclusion Criteria: - 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 - 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. --- V600E ---

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 Inclusion Criteria: - 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 - 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 Exclusion Criteria: - 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 - 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. --- V600E ---



HPO Nodes