This phase II trial tests how well vemurafenib and cobimetinib work in treating patients with high risk differentiated thyroid carcinoma with BRAFV600E mutation, in preparation for radioactive iodine therapy. Vemurafenib and cobimetinib are used in patients whose cancer has a mutated (changed) form of a gene called BRAF. They are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving vemurafenib and cobimetinib may work better to treat patients with high risk differentiated thyroid carcinoma with BRAFV600E mutation, in preparation for radioactive iodine therapy.
Documented informed consent of the participant and/or legally authorized representative
Willingness to be followed for about 14 months
Males or females aged ≥ 18 years at the time of informed consent
Patients with thyroid carcinoma of follicular origin (papillary, follicular or Hurthle cell)
Prior RAI treatment
Prior anti-BRAF, anti-MEK treatment such as sorafenib, dabrafenib, vemurafenib, encorafenib, binimetinib, cobimetinib, trametinib, d selumitinib and other TKIs like, lenvatinib, sunitinib, axitinib, cabozantenib, vandatinib, pazopanib use
Low to intermediate risk differentiated thyroid cancer (DTC) cases (not having the high-risk features as described above)
RAI contraindication
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Cobimetinib
DrugGiven PO
Computed Tomography
Procedure/SurgeryUndergo CT scan
Diagnostic Imaging
Procedure/SurgeryUndergo I-123 diagnostic scan
I-131 Uptake Test
Procedure/SurgeryUndergo I-131 whole body scan
Iodine I-131
RadiationGiven PO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo PET scan
Recombinant Thyrotropin Alfa
Biological/VaccineGiven IM
Ultrasound Imaging
Procedure/SurgeryUndergo neck ultrasound
Vemurafenib
DrugGiven PO
Patients who achieve excellent or indeterminate response with vemurafenib and cobimetinib treatment prior to radioactive iodine therapy
Excellent and indeterminate responses are defined by 2015 American Thyroid Association Management Guildelines for Differentiated Thyroid Cancer: * Excellent: Negative imaging and either suppresed thyroglobulin \< 0.2 ng/mL or TSH-stimulated thyroglobulin \< 1 ng/mL * Indeterminate: Nonspecific findings on imaging studies, faint uptake in thyroid bed on RAI scans, nonstimulated thyroglobulin detectable, but \<1 ng/mL, stimulated thyroglobulin detectable but \<10 ng/mL or thyroglobulin antibodies stable or declining in the absence of structural or functional disease
Proportion of patients who achieve increased iodine incorporation to a predicted lesion absorbed dose of 2000 cGy with I-131 dose of ≤ 300 mCi
Incidence of treatment related adverse events
Will be summarized by type, severity (by Common Terminology Criteria for Adverse Events version 5.0 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
Progression free survival
From initiation of study therapy to the first observation of disease relapse/progression or death from any cause, whichever occurs first.
Changes in thyroglobulin levels
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
