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) (MATCH Substudy)
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.
|
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). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible;
|
|
|
|
Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria:
|
|
|
|
Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
|
|
Treatment-refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensive therapy
|
|
Patients with a diagnosis of metastatic melanoma from a cutaneous, acral, mucosal, or unknown primary site are excluded;
|
|
|
|
Patients with a diagnosis of papillary thyroid cancer are excluded;
|
|
|
|
Patients with a diagnosis of colorectal adenocarcinoma are excluded;
|
|
|
|
Patients with a diagnosis of non-small cell lung cancer are excluded;
|
|
|
|
Patients with a history of interstitial lung disease or pneumonitis are excluded
|