Thyroid Cancer Clinical Trials

About Thyroid Cancer trials

Thyroid cancer trial eligibility depends heavily on histologic subtype and molecular testing. Differentiated thyroid cancer (DTC) — papillary, follicular, and Hürthle-cell (oncocytic) — accounts for most cases. Poorly differentiated thyroid carcinoma (PDTC) sits between differentiated and anaplastic disease and appears in trials either grouped with radioactive-iodine-refractory DTC or handled on its own. Medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) are biologically distinct and are usually trialed separately. The molecular markers that most often gate trials are BRAF V600E (common in papillary thyroid cancer and present in a subset of anaplastic disease — roughly a quarter of ATC — where BRAF testing is specifically advised); RET, where fusions occur in some papillary/differentiated tumors while point mutations drive many medullary cancers (MTC is generally tested for RET pathogenic variants, and hereditary MTC is associated with the MEN2A and MEN2B syndromes); the NTRK1/NTRK2/NTRK3 fusions; the RAS family (NRAS, HRAS, and KRAS, more typical of follicular and poorly differentiated tumors); and TERT promoter mutations, which are associated with more aggressive, frequently RAI-refractory disease. Testing is generally done on a tumor biopsy or thyroidectomy specimen; in medullary cancer, calcitonin and CEA are useful for diagnosis and monitoring.

Trial activity groups by subtype and by driver. Many DTC trials enroll patients whose disease has become radioactive-iodine (RAI)–refractory, the population with the greatest unmet need. Genotype-directed trials are organized around a single driver. RET-altered disease: selpercatinib is FDA-approved for RET-mutant MTC and RET fusion–positive thyroid cancer; pralsetinib remains relevant for RET fusion–positive disease and as a prior-therapy variable, though its U.S. RET-mutant MTC indication was withdrawn in 2023. BRAF V600E–mutant disease: dabrafenib plus trametinib is FDA-approved for BRAF V600E–mutant ATC that is unresectable or metastatic. NTRK fusion–positive disease: larotrectinib and entrectinib — and more recently repotrectinib — are active in a tumor-agnostic setting that includes thyroid. Some tumor-agnostic basket trials also enroll thyroid patients on the basis of biomarker alone. MTC trials frequently separate RET-mutant from RET-wild-type disease. Because several targeted therapies are already approved in thyroid cancer, a growing share of trials focus on options after prior targeted therapy or on new combinations.

Beyond biomarkers, thyroid trial eligibility commonly turns on subtype (DTC, PDTC, MTC, or ATC) and, for differentiated disease, on iodine status. RAI status is the key DTC eligibility fork: trials may ask whether disease is RAI-avid, RAI-refractory, RAI-ineligible, progressive after RAI, or progressive after prior VEGFR-targeted therapy (for example, cabozantinib is used after prior anti-VEGFR therapy such as lenvatinib or sorafenib). Prior systemic therapy is frequently a gate — many trials require or exclude specific prior tyrosine kinase inhibitors (lenvatinib, sorafenib, cabozantinib, vandetanib, selpercatinib, pralsetinib) or prior NTRK inhibitors (larotrectinib, entrectinib, repotrectinib). Measurable disease by RECIST, ECOG performance status of 0–2, and adequate organ function are typical requirements. One practical note: AJCC staging is age- and subtype-dependent — for differentiated thyroid cancer, patients under 55 can only be stage I or II, and all anaplastic thyroid cancer is stage IV — so a trial's stage language may not line up with the stage on your pathology report; check the specific eligibility criteria rather than relying on stage alone.

Biomarkers tested in Thyroid Cancer trials

These are the molecular markers most commonly required or evaluated in Thyroid Cancer eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.