Dabrafenib With or Without Trametinib in Treating Patients With Advanced Differentiated Thyroid Cancer

Inclusion Criteria

• Patients must have histologically or cytologically confirmed papillary thyroid cancer, follicular thyroid cancer (tall cell variant, insular thyroid cancer, follicular variant of papillary thyroid cancers, poorly differentiated thyroid cancer or any of the above mixed histology will be allowed)
• Presence of BRAF mutation in tumor tissue
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; malignant lymph nodes will be considered measurable if they are >= 15 mm in short axis
• Patients must have progressive disease within the thirteen months prior to study entry; progressive disease is as defined in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, which is at least a 20% increase in the sum of diameters of target lesions and the sum must also demonstrate an absolute increase of at least 5 mm; the appearance of one or more new lesions is also considered progressive disease
• Patients are willing to have tumor biopsy pre-study and at 4 weeks on study (fine needle aspiration or core biopsy) if patient has biopsy-accessible tumors as determined by investigator
• Patients must have disease that is refractory (unresponsive) to radioactive iodine (RAI) treatment as defined by one of the following:
• One or more measurable lesions that do not demonstrate RAI uptake
• One or more measurable lesions progressive by RECIST 1.1 within 12-months of prior RAI therapy
• Cumulative RAI dose of > 600 mCi
• Prior therapy allowed:
• Patients may have been previously treated with up to three regimens of oral multikinase inhibitors, including sorafenib, sunitinib and pazopanib
• Patients may have been previously treated with external beam radiation or cytotoxic chemotherapy therapy
• Eastern Cooperative Oncology Group (ECOG) performance status = = 60%)
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin = = institutional lower limit of normal
• Patient must have a calcium phosphate product (CPP) = 21 mm Hg as measured by tonography
• Patients with a known history of glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Patients with class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
• Abnormal cardiac valve morphology (subjects with minimal abnormalities, can be entered on study with approval)
• Corrected QT (QTc) interval greater than or equal to 480 msecs (>= 500 msec for subjects with bundle branch block)
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women and nursing women are excluded from this study
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• Subjects with a history of pneumonitis or interstitial lung disease
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within the past 6 months
• History of uncontrolled arrhythmias; subjects with controlled atrial fibrillation for > 1 month prior to study day 1 are eligible