Brief Summary
This prospective, multi-centre, open label, non-randomised phase II trial aims restore radioiodine sensitivity in patients with NRAS or BRAFV600E mutant refractory thyroid cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.
Participants will be treated with Trametinib +/- Dabrafenib tyrosine kinase inhibitors for a period of 30 days, restoration of sensitivity will be monitored using 18F-FDG-PET & I-124 PET imagingtests that create detailed images of areas inside the body.
Intervention / Treatment
- Drug: Dabrafenib 75 MG
- Drug: Trametinib 2 MG
Inclusion Criteria
- Histologically-confirmed differentiated (including poorly differentiated) thyroid cancer that is either locally advancedat a late stage, far along or metastatic.
- Age > 18 years.
- Life expectancy > 12 weeks.
- Documented radiological progression by RECIST 1.1 in last 12 months.
- Radioiodine refractory (at least one of):
- one measurable lesion without radioiodine uptake on 131I scan,
- at least one measurable lesion that had progressed by RECIST criteria within 12 months of 131I therapy despite 131I avidity at time of treatment, or
- cumulative treatment with >24 GBq (600 mCi) of 131I.
- At least one evaluable lesion as per RECIST v1.1 that has not been treated with local radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells within 3 months prior to the first dosethe amount of medication taken of TKI. Irradiated lesions can only be included as an evaluable lesion if it has shown radiological progression as per RECIST v1.1 on subsequent imaging following irradiation.
- NRAS or BRAF V600E mutation tested by NGS in a NATA accredited laboratory or by recognised sequencing platform.
- ECOG 0-1.
- Informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
- Adequate haematological and biochemical parameters:
- Haemoglobin ≥ 9g/dL
- Neutrophilsa type of white blood cell that act as a first responder to infections in the body ≥ 1.5 x 109/L
- Plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding ≥ 100 x 109/L
- INR ≤ 1.4
- Serum Creatinine ≤ 1.3 x ULN
- Estimated Creatinine Clearance ≥ 30 ml/min (by Cockcroft Gault Formula)
- Serum ALT and AST ≤ 2.5 x ULN
- Serum Total Bilirubin ≤ 1.5 x ULN.
- TSH suppression <0.1mU/L or otherwise consistent with 2015 ATA Guidelines on Thyroid Cancer