BRAF-mutated anaplastic thyroid cancer MedDRA version: 21.1 Level: LLT Classification code 10043745 Term: Thyroid neoplasm malignant System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tafinlar
Pharmaceutical Form: Capsule, hard
Trade Name: Mekinist
Pharmaceutical Form: Tablet
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: 1. Informed consent. 2. Age over 18 years old. 3. World Health Organization (WHO) Performance Status 0 or I. 4. Histologically confirmed ATC (centrally reviewed). 5. Confirmed presence of BRAFV600E/K mutation in primary tumor tissue. 6. No distant metastases (M0). 7. Free or secured airway. 8. Able to swallow pills. 9. Patients must have undergone complete disease staging including: PET-CT scan and CT-neck/thorax/abdomen. 10. No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies). 11. No prior radiotherapy to site of interest. 12. 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 50 mL/min/1.73m2. 13. Absence of additional severe and/or uncontrolled concurrent disease. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. No informed consent. 2. History of cancer within 2 years from diagnosis of ATC (exception: basal cell skin cancer, in situ carcinoma). 3. Poorly differentiated transformation of previous differentiated thyroid cancer. 4. Presence of distant metastases. 5. 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. 6. 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. 7. Pregnancy or nursing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This study aims to increase the number of patients that undergo a successful R0 tumor resection after neo-adjuvant BRAF/MEK inhibitor treatment.;Secondary Objective: 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 - Whether neo-adjuvant and adjuvant treatment with dabrafenib/trametinib influences quality of life ;Primary end point(s): Primary endpoint of the study will be R0 resection rate (efficacy);Timepoint(s) of evaluation of this end point: - In the interim analysis after inclusion of 7 patients, >12 weeks after start neo-adjuvant therapy - In the final analysis after inclusion of 20 patients (if study not ended prematurely), >12 weeks after start neo-adjuvant therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a. Treatment limiting acute toxicity, grade 3-4 according to CTCAE version 5.0 b. 30 day postoperative surgical complications c. Histopathological response d. Locoregional control at 3 months, 6 months, 1 year and 2 years e. Distant metastases at 3 months, 6 months, 1 year and 2 years f. Overall survival g. Quality of life at baseline, 3 months, 6 months and 1 year ;Timepoint(s) of evaluation of this end point: After inclusion of the last patient: a. After treatment, >52 weeks after start neo-adjuvant therapy b. >30 days after surgical resection c. >30 days after surgical resection d. >3 months, 6 months, 1 year and 2 years after start neo-adjuvant therapy e. >3 months, 6 months, 1 year and 2 years after start neo-adjuvant therapy f. After last follow-up, >5 years after start neo-adjuvant therapy g. >3 months, 6 months, 1 year and 2 years after start neo-adjuvant therapy | — |
Countries
Netherlands
Contacts
Public Contactdr. H.W. Kapiteijn
Leiden University Medical Center
Outcome results
None listed