Medullary Thyroid Cancer (MTC) Clinical Trials

Medullary thyroid cancer (MTC) arises from the parafollicular C cells of the thyroid gland, which produce calcitonin. Unlike the more common papillary and follicular thyroid cancers that arise from thyroid follicular cells, MTC has distinct biology, treatment, and prognosis. Serum calcitonin and carcinoembryonic antigen (CEA) serve as tumor markers for diagnosis and monitoring.

The most common symptoms of Medullary Thyroid Cancer include A lump or nodule in the neck, often painless, Hoarseness or voice changes if the tumor presses on the recurrent laryngeal nerve, Difficulty swallowing (dysphagia), Diarrhea, sometimes severe, from calcitonin excess, Flushing in advanced disease, among others. Approximately 1,000-1,200 new cases per year in the U.S.; 2-4% of all thyroid cancers. Symptoms can range from mild to severe and may vary between individuals.

Trial Friend lists all active clinical trials for Medullary Thyroid Cancer from ClinicalTrials.gov, with eligibility criteria translated into plain English. Patients can filter by trial phase and recruitment status, search by location, and use the Match Me tool to score trials against their profile. If you have advanced or metastatic MTC, the most important first step is RET mutation testing. For suspected hereditary cases, germline RET testing identifies the specific mutation and informs treatment and family screening.

Three targeted therapies are FDA-approved for advanced medullary thyroid cancer. Selpercatinib (Retevmo) is a selective RET inhibitor approved for RET-mutant MTC in adults and children 2 years and older. Vandetanib (Caprelsa) is a multi-kinase inhibitor approved for symptomatic or progressive MTC that cannot be removed by surgery or has spread, and cabozantinib (Cometriq capsules) is approved for progressive, metastatic MTC. Selective RET inhibitors are now generally preferred due to better tolerability. Pralsetinib (Gavreto) was previously approved for RET-mutant MTC under accelerated approval, but that use was withdrawn in June 2023 because the confirmatory trial was not feasible, not because of new safety or efficacy data. Gavreto remains approved for RET fusion-positive thyroid cancer and lung cancer. Always consult your endocrinologist or oncologist about which therapy is right for your situation.

Medullary thyroid cancer arises from the parafollicular C cells of the thyroid gland, which produce the hormone calcitonin. About 75% of MTC cases are sporadic (non-hereditary), caused by somatic RET mutations acquired in the tumor, most commonly RET M918T. The remaining 25% are hereditary, caused by germline RET proto-oncogene mutations inherited from a parent. Hereditary MTC occurs as part of Multiple Endocrine Neoplasia type 2 (MEN 2A or MEN 2B) or as Familial MTC (FMTC). The specific RET codon mutation determines cancer aggressiveness and guides the recommended age for prophylactic thyroidectomy in mutation carriers.

RET proto-oncogene testing is essential for all MTC patients. Approximately 25% of MTC cases are hereditary, caused by germline RET mutations. Genetic testing identifies which specific codon mutation is present, which predicts cancer aggressiveness and determines whether family members need cascade screening. Patients with MEN 2A or MEN 2B carry RET mutations that also increase risk for pheochromocytoma and hyperparathyroidism. Children of RET mutation carriers have a 50% chance of inheriting the mutation and should be tested early, since prophylactic thyroidectomy before cancer develops can be lifesaving. Somatic RET mutation testing of tumor tissue is also important for selecting targeted therapies like selpercatinib.

Eligibility for Medullary Thyroid Cancer clinical trials depends on factors like age, diagnosis, treatment history, and overall health. Each trial sets its own inclusion and exclusion criteria. Trial Friend translates these requirements from medical language into plain English so patients can review them more easily. The Match Me tool can score your profile against active trials to help identify studies that may be a fit.

Participating in a Medullary Thyroid Cancer clinical trial typically involves scheduled visits, medical tests, and close monitoring by a research team. Depending on the study phase, you may receive an investigational treatment, a placebo, or the current standard of care. Trials may last from a few weeks to several years. Study participation is voluntary, and you can withdraw at any time.

Medullary thyroid cancer clinical trials commonly exclude patients currently on other RET-targeted therapies (selpercatinib, pralsetinib, vandetanib, cabozantinib) without adequate washout periods, typically 2-4 weeks. Trials testing selective RET inhibitors may exclude prior selective RET inhibitor use. QT-prolonging medication combinations are frequently excluded in vandetanib-containing regimens. Trial Friend's medication conflict checker scans each trial's exclusion criteria against common MTC medications including RET inhibitors, multi-kinase inhibitors, thyroid hormone replacement, and supportive care drugs. The checker flags the specific drug, the trial's exclusion language, and a confidence level so you can discuss timing with your oncologist.

Key questions to ask your oncologist about MTC clinical trials include: Has my tumor been tested for specific RET mutations, and does the mutation type affect which trials I qualify for? If I'm currently on vandetanib or cabozantinib, what washout period would I need before switching to a selective RET inhibitor trial? Are there trials combining RET inhibitors with other therapies for patients whose disease has progressed on selpercatinib? What are my current calcitonin and CEA doubling times, and do they indicate I should consider a trial now or can I wait? For hereditary MTC patients: have my family members been offered RET genetic testing and cascade screening?