A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib (XL184) in Subjects With Radioiodine-Refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy

XL184-311

The objective of this study is to evaluate the effect of cabozantinib compared with placebo on progression free survival (PFS) and objective response rate (ORR) in subjects with Radioiodine-Refractory Differentiated Thyroid Cancer (DTC) who have progressed after prior vascular endothelial growth factor receptor (VEGFR)-Targeted therapy.

2018-10-05

2020-08-19

2024-12-01

Active (not recruiting)

Early phase I

187

Inclusion Criteria: 1. Histologically or cytologically confirmed diagnosis of Differentiated Thyroid Cancer (DTC) 2. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 3. Previously treated with or deemed ineligible for treatment with Iodine- 131 for differentiated thyroid cancer (DTC) 4. Previously treated with at least one of the following vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitor (TKI) agents for DTC: lenvatinib or sorafenib. Note: Up to two prior VEGFR-targeting TKI agents are allowed 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 Exclusion Criteria: 1. Prior treatment with any of the following: Cabozantinib; Selective small-molecule v-raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase inhibitor; More than 2 VEGFR-targeting TKI agents; More than 1 immune checkpoint inhibitor therapy; 1 systemic chemotherapy regimen (given as single agent or in combination with another chemotherapy agent) 2. Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before randomization 3. Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before randomization 4. Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before randomization. 5. Known brain metastases or cranial epidural disease unless adequately treated

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of cabozantinib in subjects with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) after prior vascular endothelial growth factor receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy. Cabozantinib-matched placebo will be given in the control arm to blind (mask) study treatment. Approximately 300 eligible subjects will be randomized in a 2:1 ratio to receive either cabozantinib or placebo. After the primary efficacy endpoints have been analyzed and sufficient data have been collected to adequately evaluate all study endpoints to establish, for regulatory purposes, the safety and efficacy profile of the experimental drug within this study, the study will transition to an open label Maintenance Phase.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'Study treatment assignment will be unknown to the subjects, investigators, study centers, Sponsor, and any Contract Research Organization affiliated with the study other than those authorized to access treatment assignment for regulatory safety reporting and submission processes, interactive response technology (IRT) system administration, and drug supply management. Cabozantinib-matched placebo will be packaged and color-, size-, and shape-matched to be indistinguishable from cabozantinib. Individual study treatment assignment will be unblinded and information provided to the Investigators upon request for subjects with radiographic progressive disease (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 confirmed by the blinded independent radiology committee (BIRC).', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 187, 'type': 'ACTUAL'}}

2024-03-22