Trametinib in Combination With Paclitaxel in the Treatment of Anaplastic Thyroid Cancer

Exclusion Criteria

• •Patients who have had chemotherapy or radiotherapy within 7 days of starting treatment.
• •Symptomatic or untreated brain metastases, leptomeningeal disease, or spinal cord compression
• •History of interstitial lung disease or pneumonitis
• •History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
• •* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension)
• •* Visible retinal pathology as assessed by ophthalmic exam that is considered a high risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure \>21 mm Hg
• •History or evidence of cardiovascular risk including any of the following:
• •* LVEF\<LLN
• •* A QT interval corrected for heart rate using the Bazett's formula QTcB ≥480 msec
• •* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for \>30 days prior to -enrollment are eligible)
• •* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
• •* History or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
• •* Treatment-refractory hypertension defined as a blood pressure of systolic \>150 mmHg and/or diastolic \>90 mmHg which cannot be controlled by anti-hypertensive therapy
• •* Known cardiac metastases
• •Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection, which will be allowed) HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with trametinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• •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
• •Any condition that may impair the ability to absorb oral medications/investigational product including: prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel; active peptic ulcer disease; and malabsorption syndrome
• •Any major surgery within 21 days prior to enrollment.
• •Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to taxanes and drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO)
• •Current use of a prohibited medication. The following medications or non-drug therapies are prohibited:
• •* Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
• •* Because the composition, PK, and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra \[ma huang\], gingko biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, or ginseng)