Clinical Trial in RAI-Refractory Thyroid Carcinoma Evaluating BRAF & MEK Blockade for Re-differen… (NCT04554680) | Clinical Trial Compass
UnknownPhase 2
Clinical Trial in RAI-Refractory Thyroid Carcinoma Evaluating BRAF & MEK Blockade for Re-differentiation Therapy
Singapore5 participantsStarted 2020-12-30
Plain-language summary
Progressive and metastatic thyroid cancer patients, who no longer respond to radioactive iodine (RAI), are currently treated with long term tyrosine kinase inhibitors to control tumor growth. The investigators will study the effect of short term oral anti-cancer drug combination, called dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), in improving thyroid cancer RAI absorption that can potentially lead to tumor shrinkage response. To assess for suitability, participant's thyroid cancer tissue taken at the time of surgery will be tested for DNA changes, such as BRAFV600E, RAS, or MEK mutations.
Based on experimental studies, the response to these medications could occur within 1 week of treatment. So in the study, the investigators will find out whether participant's cancer would respond to 1 week of treatment with these medications rather than the 1 month duration of treatment in previous re-differentiation clinical trials. After 1 week of treatment with dabrafenib and trametinib, iodine absorption I-124 PET-CT scan will predict if the cancer will respond to RAI. If iodine absorption is insufficient on the scan, treatment with dabrafenib and trametinib will be continued for a total of 4 weeks. Then iodine absorption response of participant's cancer will be assessed on I-124 PET-CT scan again. If the iodine absorption is good at 1 week or 4 weeks, the investigators will treat the participant with thyroid cancer using RAI.
The 1-week treatment regime can potentially save cost, avoid drug toxicity with prolonged treatment, and prevent drug resistance that can occur with longer treatment period.
Who can participate
Age range21 Years – 99 Years
SexALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Participants must be at least 21 years of age on the day of signing informed consent.
✓. The participant (or legally acceptable representative if applicable) provides written consent for the trial.
✓. Eastern Cooperative Oncology Group (ECOG) performance status \< 2
✓. . The histology of the thyroid carcinoma for inclusion includes any of the following:
✓. Patients with a thyroid carcinoma of follicular cell origin with mutation involving MAPK signalling pathway, including BRAFV600E mutation or RAS mutation detected in a Clinical Laboratory Improvement Amendments (CLIA)-certified or US Food and Drug Administration-approved assay.
✓. The patients need to fulfil one of the following criteria for RAI-refractory disease (Tuttle et al, 2019;):
✓. No 131-I uptake is present on a diagnostic 131-I scan
✓. No 131-I uptake is present on a 131I scan performed several days after 131-I therapy
Exclusion criteria
What they're measuring
1
The proportion of participants attaining at least one tumor lesion with lesional dosimetry of >=2000 cGy with I-131 dose of =<300 mCi.
Timeframe: 1 month after start of dabrafenib and trametinib
✕. Exceeded cumulative I-131 treatment dose of \>600mCi
✕. Treatment with I-131 therapy 6 months before study treatment.
✕. G6PD deficiency due to risk of haemolytic anaemia with dabrafenib
✕. Had received prior systemic anti-cancer therapy, including investigational agents within 2 weeks prior to randomisation.
✕. Had received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities.
✕. Patients who have not recovered from adverse events related to prior therapy for cancer to Common Terminology Criteria for Adverse Events (CTCAE) 4.03 grade 2 or less, except for alopecia.
✕. Patients with a history of other active malignancy requiring cancer treatment.