This phase II MATCH treatment trial identifies the effects of trametinib and dabrafenib in patients whose cancer has genetic changes called BRAF V600 mutations. Dabrafenib may stop the growth of cancer by blocking BRAF proteins which may be needed for cell growth. Trametinib may stop the growth of cancer cells by blocking MEK proteins which, in addition to BRAF proteins, may also be needed for cell growth. Researchers hope to learn if giving trametinib with dabrafenib will shrink this type of cancer or stop its growth.
Name: Dabrafenib Mesylate
Name: Trametinib Dimethyl Sulfoxide
Description: ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.
Measure: Objective response rate (ORR) Time: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registrationDescription: OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
Measure: Overall survival (OS) Time: Assessed every 3 months for =< 2 years and every 6 months for year 3Description: PFS is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.
Measure: Progression free survival (PFS) Time: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registrationAllocation: N/A
Single Group Assignment
There are 4 SNPs
PFS will be estimated using the Kaplan-Meier method.. Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E --- --- V600K --- --- V600R --- --- V600D ---
However, if the results of previous RAS testing are known, they must be used in assessing eligibility Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E --- --- V600K --- --- V600R --- --- V600D ---
MATCH Treatment Subprotocol H: Phase II Study of Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E or V600K Mutations (Excluding Melanoma, Thyroid Cancer, Colorectal Adenocarcinoma, and Non-Small Cell Lung Cancer). --- V600E ---
PFS will be estimated using the Kaplan-Meier method.. Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E ---
However, if the results of previous RAS testing are known, they must be used in assessing eligibility Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E ---
MATCH Treatment Subprotocol H: Phase II Study of Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E or V600K Mutations (Excluding Melanoma, Thyroid Cancer, Colorectal Adenocarcinoma, and Non-Small Cell Lung Cancer). --- V600E --- --- V600K ---
PFS will be estimated using the Kaplan-Meier method.. Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E --- --- V600K ---
However, if the results of previous RAS testing are known, they must be used in assessing eligibility Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E --- --- V600K ---
PFS will be estimated using the Kaplan-Meier method.. Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E --- --- V600K --- --- V600R ---
However, if the results of previous RAS testing are known, they must be used in assessing eligibility Inclusion Criteria: - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol - Patients must have a BRAF V600E or, V600K, V600R or V600D mutation, or another aberration, as identified via the MATCH Master Protocol - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to registration to treatment - Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN). --- V600E --- --- V600K --- --- V600R ---