Clinical Trial in RAI-Refractory Thyroid Carcinoma Evaluating BRAF & MEK Blockade for Re-differentiation Therapy
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|ClinicalTrials.gov Identifier: NCT04554680|
Recruitment Status : Unknown
Verified August 2020 by National University Hospital, Singapore.
Recruitment status was: Recruiting
First Posted : September 18, 2020
Last Update Posted : March 5, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Thyroid Cancer||Drug: dabrafenib and trametinib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Clinical Trial in Radioactive Iodine-Refractory Advanced Thyroid Carcinoma Evaluating BRAF & MEK Blockade Therapy for Re-differentiation- Applying a Novel Time-Dependent Concept|
|Actual Study Start Date :||December 30, 2020|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||April 2022|
Experimental: Treatment Group
Patients with progressive, metastatic or locally advanced, unresectable radioiodine (RAI)-refractory thyroid cancer of follicular cell origin with mutation involving MAPK signalling pathway, including BRAFV600E mutation or RAS mutation.
Drug: dabrafenib and trametinib
Participants will receive systemic therapy in the form of oral tablet dabrafenib 150mg twice a day & oral tablet trametinib 2mg once a day for 1 or 4 weeks.
Pre- & post-systemic therapy assessment of tumor iodine absorption is done using I-124 PET CT scan. Participants are prepared for this scan with intramuscular injection of thyrogen 0.9mg on 2 consequent days, followed by I-124 PET-CT scan over the next 3 days for tumoral lesional dosimetry.
Participants are then started on systemic therapy for 1 week, followed by I-124 PET-CT scan. If at least one tumor site can attain adequate dosimetry, RAI (I-131) treatment under thyrogen stimulation will be considered. Systemic therapy will be stopped 3 days after I-131.
If after 1 week of systemic therapy, tumors do not reach dosimetry criteria, participants will be continued on systemic therapy for a total of 4 weeks duration, followed by I-124 PET-CT scan. If tumor can attain adequate dosimetry, I-131 treatment will be considered.
- The proportion of participants attaining at least one tumor lesion with lesional dosimetry of >=2000 cGy with I-131 dose of =<300 mCi. [ Time Frame: 1 month after start of dabrafenib and trametinib ]
The primary endpoint can be considered attained in both groups of participants:
- those that attain target lesional dosimetry after 1 week of therapy
- those that attain target lesional dosimetry after 4 weeks of therapy
- Progression-free survival and overall survival [ Time Frame: From the start of assessment until study completion, an average of 2 years ]
- Best tumor response as assessed by RECIST criteria [ Time Frame: From the start of assessment until study completion, an average of 2 years ]
- Change in serum thyroglobulin level after radioactive iodine (RAI) treatment compared to baseline, pre-treatment level [ Time Frame: 6 months after RAI treatment ]
- The proportion of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: From the start of assessment until study completion, an average of 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04554680
|Contact: Samantha, Peiling Yang, MBBS, MRCP||(+65) 6779 email@example.com|
|National University Hospital||Recruiting|
|Contact: Samantha, Peiling Yang, MBBS, MRCP (+65) 6779 5555 firstname.lastname@example.org|
|Principal Investigator: Samantha, Peiling Yang, MBBS, MRCP|
|Sub-Investigator: Kelvin, Siu Hoong Loke, MBBS, MRCP|