Table 3.
Overview of currently ongoing clinical trials studying pazopanib, cabozantinib, and vandetanib in MTC [52].
| Drug | Title | Design | Objective | Status | Results |
|---|---|---|---|---|---|
| Pazopanib | A Phase II Study of GW 786034 (Pazopanib) in Advanced Thyroid Cancer NCT00625846 | Interventional Open label | To establish safety and efficacy of pazopanib in Differentiated thyroid cancer (DTC), Medullary thyroid cancer (MTC), and Anaplastic thyroid cancer (ATC), how the drug impacts VEGF plasma levels and the changes is thyroglobulin and its relationship with tumor response. | Active, Not recruiting | The study found positive partial response rates in DTC, but has no overall survival (OS) measure. Adverse effects (AEs) occurred in 43% but generally mild. It showed to be a positive treatment option [53]. |
| Cabozantinib | A Randomized, Double-blind Study To Evaluate the Efficacy and Safety of Cabozantinib (XL184) at 60 mg/Day Compared to a 140 mg/Day in Progressive, Metastatic Medullary Thyroid Cancer Patients NCT01896479 | Interventional Double-blind Randomized | To study the efficacy and safety of cabozantinib when comparing to different doses: 60 mg and 140 mg with placebo. Efficacy measures are progression free survival and overall response rate. Safety measures is a comparison between fewer adverse effects and the efficacy measures. | Recruiting | − |
| An Open-Label, Expanded Access Study of Cabozantinib (XL184) in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer NCT01683110 | Expanded access Open Label | Provide access to cabozantinib | Approved for marketing | − | |
| An International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 Versus Placebo in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer NCT00704730 | Interventional Double-blind Randomized | This study is comparing efficacy measures such as progression-free survival, overall survival and objective response rate between patients receiving cabozantinib and placebo. | Unknown, has results | The study found a statistically significant increase in Progression free survival (PFS) using cabozantinib compared to placebo, an objective response rate of 28% (higher for RET M918T positive subgroup) and an improved OS, although not significantly better than placebo [42,43]. | |
| A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies NCT00215605 | Interventional Open label | This study is evaluating the safety, tolerability, maximum tolerated dose and dose-limiting toxicity of cabozantinib. It also evaluates plasma pharmacokinetics and renal elimination. Measurements include progression-free survival and tumor response. | Completed | 49% of patients with MTC showed tumor shrinkage and 68% of these showed stable disease for over 6 months. Of all patients included, 90% experienced AEs, but 43% were of grade 1 or 2. The drug was considered to have a satisfactory safety profile [34] | |
| A Phase 1 Study of XL184 (Cabozantinib) in Children and Adolescents With Recurrent or Refractory Solid Tumors, Including CNS Tumors NCT01709435 | Interventional Open label | It is evaluating maximum tolerated dose and recommended phase II dose of cabozantinib in children with solid tumors incl. childhood thyroid gland medullary carcinomas. They also describe toxicities, pharmacokinetics and evaluate overall survival. | Active, Not recruiting | − | |
| Phase 2 Trial of XL184 (Cabozantinib) an Oral Small-Molecule Inhibitor of Multiple Kinases, in Children and Young Adults With Refractory Sarcomas, Wilms Tumor, and Other Rare Tumors NCT02867592 | Interventional, Open label | Determine the objective response rate, toxicities, and pharmacokinetics of cabozantinib in children and young adults with rare tumors. | Recruiting | ||
| Vandetanib | European, Observational, Prospective Study to Evaluate the Benefit/Risk of Vandetanib in RET Mutation Negative and Positive Patients With Symptomatic, Aggressive, Sporadic, Unresectable, Locally Advanced/Metastatic Medullary Thyroid Cancer NCT01945762 | Observational | Assessment of the risk/benefit of 300 mg/d vandetanibin RET positive and RET negative patients with MTC. | Recruiting | |
| Phase I/II Trial of Vandetanib (ZD6474, ZACTIMA) in Children and Adolescents With Hereditary Medullary Thyroid Carcinoma NCT00514046 | Interventional | Investigation of activity of vandetanib in children and adolescents with MTC caused by multiple endocrine neoplasia genetic disorder. Assessment of safety, tolerability, and survival in the study group. | Active, not recruiting | ||
| A Randomized, Int., Open-Label Phase III Study to Assess the Effect of a Patient Outreach Program on the Percentage of Time Patients With Locally Advanced or Metastatic MTC Experience Grade 2 or Higher AEs in the First 12 Months of Treatment With Vandetanib NCT01298323 | Randomized, Open label | Determine if contacting patients with MTC more frequently results in earlier detection and treatment of signs and symptoms of AEs during the first 12 months on vandetanib treatment. | Active, not recruiting | ||
| An International, Randomised, Double-Blind, Two-Arm Study To Evaluate The Safety And Efficacy Of Vandetanib 150 And 300mg/Day In Patients With Unresectable Locally Advanced Or Metastatic Medullary Thyroid Carcinoma With Progressive Or Symptomatic Disease NCT01496313 | Interventional, Randomized, Double-blind | Comparison of safety and efficacy of 150 and 300 mg/d vandetanib in patients with MTC. | Active, not recruiting |