NEO- and Adjuvant Targeted Therapy in Braf-mutated Anaplastic Cancer of the Thyroid (NEO-ATACT Study)

Prior treatment

• Poorly differentiated transformation of previous differentiated thyroid cancer.

Other illness

• History of cancer within 2 years from diagnosis of ATC (exception: basal cell skin cancer, in situ carcinoma).
• Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events
• History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.

Other

• No informed consent.
• Presence of distant metastases.
• Pregnancy or nursing.

• Informed consent.
• Age over 18 years old.
• World Health Organization (WHO) Performance Status 0 or I.
• Histologically confirmed ATC (centrally reviewed).
• Confirmed presence of BRAFV600E/K mutation in primary tumor tissue.
• No distant metastases (M0).
• Free or secured airway.
• Able to swallow pills.
• Patients must have undergone complete disease staging including: PET-CT scan and CT-neck/thorax/abdomen.
• No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies).
• No prior radiotherapy to site of interest.
• Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 6.5 mmol/L, AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, Total bilirubin ≤ 1.5 X ULN, INR and PTT in normal range, LDH \< 2xULN. Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate \> 50 mL/min/1.73m2.
• Absence of additional severe and/or uncontrolled concurrent disease.