Manisha H Shah, MD of The James Ohio State University Comprehensive Cancer Center explains the study: Dabrafenib, Trametinib, and IMRT in Treating Patients With BRAF Mutated Anaplastic Thyroid Cancer.
Summary Brief:
This research studies how well dabrafenib, trametinib, and intensity modulated radiation therapy (IMRT) function together in the treatment of anaplastic thyroid cancer mutated in BRAF patients. Dabrafenib and trametinib can halt tumor cell growth by blocking some of the enzymes required to grow the cells. Radiation therapy uses beams of high energy to destroy tumor cells and to shrink tumours. More tumor cells may be destroyed by administering dabrafenib, trametinib, and IMRT together.
Description in detail:
OBJECTIVES OF PRIMARY:
I. To evaluate the safety and tolerability (MTD) of concomitant intensity modulated radiation therapy (IMRT) and BRAF-MEK dabrafenib and trametinib inhibitors in patients with BRAF-mutated anaplastic thyroid cancer.
OBJECTIVES TO SECONDARY:
I. Evaluation of overall target response rate, period for local recurrence progression, progression free survival and overall survival.
II . II. To evaluate pharmacokinetics during concurrent treatment with IMRT and dabrafenib plus trametinib.
III. III. To test the pharmacodynamics of dabrafenib plus induction therapy with trametinib.
IV. IV. To determine the function of dabrafenib resistance plus trametinib and radiation therapy.
OUTLINE: This is a Dabrafenib dose-escalation analysis.
INDUCTION: In the absence of disease progression and undesirable toxicity, patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) for 7 to 28 days.
OPTIONAL SURGERY: Patients with resectable disease can undergo surgery 3 days after discontinuation of dabrafenib / trametinib therapy and switch to Concurrent Radiation 14 days after surgery if surgical wound healing has occurred. All other patients, in the absence of disease progression and excessive toxicity, continue to receive dabrafenib PO BID and trametinib PO QD.
CONCURRENT RADIATION: Dabrafenib PO BID and trametinib PO QD are administered to patients within 6-7 weeks. Patients undergo strength modulated radiation therapy (IMRT) on Monday-Friday within 2.5 hours of morning dose administration of dabrafenib / trametinib administered over 6.5 weeks in the absence of disease development or inappropriate toxicity.
POST-RADIATION: In the absence of disease progression and excessive toxicity, patients receive dabrafenib PO BID and trametinib PO QD for 4 weeks.
MAINTENANCE: In the absence of disease progression and inappropriate toxicity residual disease patients receive dabrafenib PO BID and trametinib PO QD. Patients discontinue dabrafenib and trametinib 8 weeks after full response is achieved. Patients with no residual infection quit dabrafenib and trametinib, with the option to resume dabrafenib and trametinib at the time of recurrence of the disease.
Patients are followed up every 2 months for 1 year after completion of study therapy.
https://clinicaltrials.gov/ct2/show/NCT03975231