A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib in Patients With Radioiodine (RAI)-Refractory Differentiated Thyroid Cancer (DTC) Who Have Progressed After Prior VEGFR-Targeted Therapy

  • Background: Treatment options are limited for patients with RAI-refractory DTC that is resistant to VEGFR-targeted therapy. Cabozantinib inhibits receptor tyrosine kinases including VEGFR2, MET, AXL and RET which are implicated in the development of DTC, and has shown clinical activity in early phase studies of patients with RAI-refractory DTC. This study evaluates the efficacy and safety of cabozantinib in patients with RAI-refractory DTC who have progressed during or after prior VEGFR-targeted therapy. Methods: This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial. The co-primary endpoints are PFS and ORR evaluated by blinded independent radiology committee (BIRC) per RECIST v 1.1. Additional endpoints include safety, OS, quality of life, and changes in relevant biomarkers levels (e.g. thyroglobulin). Approximately 300 patients will be randomized in a 2:1 ratio to receive either cabozantinib (60 mg qd orally) or placebo. Randomization will be stratified by prior treatment with lenvatinib and age (? 65 years vs. > 65 years). Eligible patients must have a pathologic diagnosis of DTC and must have been previously treated with or deemed ineligible for treatment with iodine-131 for DTC. Patients must have received lenvatinib or sorafenib for DTC and progressed during or following treatment with a VEGFR inhibitor. Upto 2 prior VEGFR-targeting TKI agents are allowed. Patients randomized to placebo may be eligible for real time on-study crossover to cabozantinib based on BIRC confirmation of disease progression. Unblinded patients randomized to cabozantinib may continue on study treatment if there is clinical benefit per investigator.

 

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