Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer

PRIMARY OBJECTIVES: I. To assess the safety and tolerability (maximum tolerated dose \[MTD\]) of concurrent intensity modulated radiation therapy (IMRT) and BRAF-MEK inhibitors dabrafenib and trametinib in patients with BRAF-mutated anaplastic thyroid cancer. SECONDARY OBJECTIVES: I. To assess overall objective response rate, time to progression of local recurrence, progression free survival and overall survival. II. To assess pharmacokinetics during concurrent IMRT and dabrafenib plus trametinib therapy. III. To assess pharmacodynamics of dabrafenib plus trametinib induction therapy. IV. To assess mechanism of resistance to dabrafenib plus trametinib and radiation therapy. OUTLINE: This is a dose-escalation study of dabrafenib. INDUCTION: Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 7-28 days in the absence of disease progression and unacceptable toxicity. OPTIONAL SURGERY: Patients with resectable disease may undergo surgery 3 days after stop treatment of dabrafenib/trametinib, and move to Concurrent Radiation 14 days after surgery provided that surgical wound has healed. All other patients continue to receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity. CONCURRENT RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD at weeks 6-7. Within 2.5 hours of morning doses of dabrafenib/trametinib administration, patients undergo intensity modulated radiation therapy (IMRT) on Monday-Friday delivered over 6.5 weeks in the absence of disease progression or unacceptable toxicity. POST-RADIATION: Patients receive dabrafenib PO BID and trametinib PO QD for 4 weeks in the absence of disease progression and unacceptable toxicity. MAINTENANCE: Patients with residual disease receive dabrafenib PO BID and trametinib PO QD in the absence of disease progression and unacceptable toxicity. Patients stop dabrafenib and trametinib 8 weeks after achieving complete response. Patients with no residual disease stop dabrafenib and trametinib, with the option of restarting dabrafenib and trametinib at time of disease recurrence. After completion of study treatment, patients are followed up every 2 months for 1 year.