This phase II trial studies the effect of pembrolizumab, dabrafenib, and trametinib before surgery in treating patients with BRAF V600E-mutated anaplastic thyroid cancer. BRAF V600E is a specific mutation (change) in the BRAF gene, which makes a protein that is involved in sending signals in cells and in cell growth. It may increase the growth and spread of tumor cells. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Pembrolizumab, dabrafenib, and trametinib may help to control BRAF V600E-mutated anaplastic thyroid cancer when given before surgery.
Name: Conventional Surgery
Name: Dabrafenib
Name: Intensity-Modulated Radiation Therapy
Name: Pembrolizumab
Name: Quality-of-Life Assessment
Name: Trametinib
Description: Overall R0/R1 resection rate will be defined by proportion of patients who undergo successful thyroidectomy with clear (R0) or microscopically positive (R1) surgical margins. We will test the hypothesis that the R0/R1 resection rate is greater than historical rate of 5%.
Measure: Complete gross surgical resection (R0 or R1 resection) Time: Up to 5 cycles (1 cycle = 21 days)Description: OS will be measured as the time from the start of any trial treatment to death from any causes. Kaplan-Meier method will be used to estimate the median survival time across all patients and its 95% confidence intervals (CI).
Measure: Overall survival (OS) Time: Up to 72 monthsDescription: Objective tumor response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure: Tumor response Time: Up to 42 monthsDescription: PFS will be measured as the time from the start of the treatment to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by RECIST version 1.1.
Measure: Progression free survival (PFS) Time: Up to 42 monthsDescription: Surgical morbidity/complexity will be measured at enrollment, prior to surgery and at surgery. The Thyroid Neck Group Morbidity Complexity Scoring and MGH/MEE-MSK-MD Anderson (MMM) Surgical Morbidity Complexity Score are incorporated, specifying on a scale with 5 levels of complexity and morbidity of the surgery [mild (level 0), moderate (level 1), severe (level 2), very severe (level 3), and unresectable (level 4)].
Measure: Surgical morbidity/complexity Time: Up to 5 cycles (1 cycle = 21 days)Description: Frequency and severity of adverse events as a measure of safety profile for neoadjuvant concurrent administration of dabrafenib, trametinib, and pembrolizumab (DTP) will be assessed using Common Terminology Criteria for Adverse Events version 5.0.
Measure: Number of patients with adverse events as a measure of safety of neoadjuvant dabrafenib, trametinib, and pembrolizumab Time: Up to 5 cycles (1 cycle = 21 days)Description: Frequency and severity of adverse events as a measure of safety profile for concurrent administration of postoperative pembrolizumab with IMRT will be assessed using Common Terminology Criteria for Adverse Events version 5.0.
Measure: Number of patients with adverse events as a measure of safety of postoperative pembrolizumab plus IMRT Time: Over the course of adjuvant IMRT plus 2 weeks of safety follow-up, assessed up to 2 monthsDescription: Locoregional control will be measured as the time from the start of any trial treatment to the first locoregional recurrence/progression event.
Measure: Locoregional control Time: Up to 42 monthsDescription: Changes of health-related quality of life will be measured by the European Quality of Life 5 Dimension Questionnaire (EQ-5D). The EQ-5D consists of health state description and evaluation. The health state description consists of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), with each dimension specifying five levels of severity [best (1)-worst (5)]. The health state evaluation is assessed using the visual analogue scale ([worse (0)-best (100)].
Measure: Health related quality of life Time: Up to 42 monthsDescription: Symptom burden experienced by patients will be measured by the M.D. Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN) instrument.
Measure: Patient-reported symptoms Time: Up to 42 monthsAllocation: N/A
Single Group Assignment
There is one SNP
Pembrolizumab, Dabrafenib, and Trametinib Before Surgery for the Treatment of BRAF-Mutated Anaplastic Thyroid Cancer This phase II trial studies the effect of pembrolizumab, dabrafenib, and trametinib before surgery in treating patients with BRAF V600E-mutated anaplastic thyroid cancer. --- V600E ---
BRAF V600E is a specific mutation (change) in the BRAF gene, which makes a protein that is involved in sending signals in cells and in cell growth. --- V600E ---
Pembrolizumab, dabrafenib, and trametinib may help to control BRAF V600E-mutated anaplastic thyroid cancer when given before surgery. --- V600E ---
Diagnosis may include consistent with or suggestive of terminology associated with: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present - Must have a BRAFV600E mutation-positive tumor, as determined by BRAF V600E immunohistochemistry on tumor tissue, genetic/molecular testing of tumor, or cell free (cf)NDA liquid biopsy - Total bilirubin =< 1.5 x upper limit of normal (ULN). --- V600E ---