DABRAFENIB for Anaplastic thyroid cancer

Inclusion criteria

• {"criterion_text":"- Informed consent\n- No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies).\n- No prior radiotherapy to site of interest\n- 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\n- Absence of additional severe and/or uncontrolled concurrent disease\n- Age over 18 years old.\n- World Health Organization (WHO) Performance Status 0 or I.\n- Histologically confirmed ATC (centrally reviewed).\n- Confirmed presence of BRAFV600E/K mutation in primary tumor tissue.\n- No distant metastases (M0).\n- Free or secured airway\n- Able to swallow pills\n- Patients must have undergone complete disease staging including: PET-CT scan and CT-neck/thorax/abdomen"}

Exclusion criteria

• {"criterion_text":"- No informed consent.\n- History of cancer within 2 years from diagnosis of ATC (exception: basal cell skin cancer, in situ carcinoma).\n- Poorly differentiated transformation of previous differentiated thyroid cancer\n- Presence of distant metastases.\n- 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.\n- 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\n- Pregnancy or nursing"}

Primary endpoints

• {"endpoint_text":"- This study aims to increase the number of patients that undergo a successful R0 tumor resection after neo-adjuvant BRAF/MEK inhibitor treatment.","definition_or_measurement_approach":"Primary endpoint expressed as the R0 resection rate: percentage of patients undergoing a successful R0 tumour resection after neo-adjuvant BRAF/MEK inhibitor treatment (RO resection rate)."}

Secondary endpoints

• {"endpoint_text":"- To evaluatue: - Neo-adjuvant and adjuvant treatment related toxicity of dabrafenib/trametinib (according to CTCAE v. 5.0) - 30-day postoperative surgical complications - Histopathological response on neo-adjuvant treatment - Locoregional-free survival - Distant metastasis-free survival - Overall survival","definition_or_measurement_approach":"Toxicity assessed by CTCAE v5.0; 30-day postoperative surgical complications monitored as post-op complication rate; histopathological response assessed on resected specimen; locoregional-free survival, distant metastasis-free survival and overall survival measured as time-to-event outcomes (specific timepoints/analysis methods not detailed in record)."}

Other endpoints

• {"endpoint_text":"- Tertiary/exploratory objective(s): To evaluate: - Molecular and immunological responses on dabrafenib/trametinib in ATC","definition_or_measurement_approach":"Exploratory molecular and immunological response assessments (specific biomarkers, assays or timepoints not specified in the record)."}

Netherlands

Earliest CTIS Part Ii Submission Date

04-10-2024

Latest Decision Or Authorization Date

17-02-2025

Processing Time Days

136

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Leids Universitair Medisch Centrum (LUMC)

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands