Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

Inclusion Criteria

• Histologically or cytologically confirmed papillary thyroid cancer or papillary thyroid cancer with follicular elements
• No longer amenable to radioactive iodine therapy or curative surgical resection
• Tumor is no longer iodine avid
• Tumor did not respond to the most recent radioactive iodine treatment
• Patient is ineligible for further radioactive iodine therapy due to medical contraindications (e.g., lung toxicity)
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
• Evidence of disease progression (objective growth of existing tumors)
• New or enlarging measurable lesions within the past 12 months
• If the most recent imaging study is older than 12 months, patients will still be eligible if objectively measurable disease progression is associated with clinical symptoms
• Archival tumor tissue available for mutational analysis
• No known brain metastases
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 12 weeks
• WBC ≥ 3,000/µL
• ANC ≥ 1,500/µL
• Platelet count ≥ 100,000/µL
• Total bilirubin normal
• AST and ALT 450 msec or other factors that increase the risk of QT prolongation
• Arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome), including heart failure that meets NYHA class III and IV definition
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• Concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• Prior treatment with tyrosine kinase inhibitors that target RET or RAF
• Prior treatment with MEK inhibitors
• Concurrent combination antiretroviral therapy for HIV-positive patients
• Concurrent medication that can prolong the QT interval
• Other concurrent investigational agents