TriangleNCT03690388 · CITED IN SOURCE DOCUMENTS
A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2025-09-25
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Who could take part
- eligibility Criteria
- 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
- healthy Volunteers
- false
- minimum Age
- 16 Years
- sex
- ALL
- std Ages
- CHILD
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- cabozantinib (60 mg) once daily orally (qd)
- intervention Names
- Drug: Cabozantinib
- label
- Cabozantinib
- type
- EXPERIMENTAL
- description
- placebo once daily orally (qd)
- intervention Names
- Drug: Placebo
- label
- Placebo
- type
- PLACEBO_COMPARATOR
- interventions
- arm Group Labels
- Cabozantinib
- description
- Tablets containing 60-mg or 20-mg cabozantinib once daily orally.
- name
- Cabozantinib
- other Names
- XL184
- Cabometyx®
- type
- DRUG
- arm Group Labels
- Placebo
- description
- Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- intervention Model Description
- 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.
- masking Info
- masking
- TRIPLE
- masking Description
- 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).
- who Masked
- PARTICIPANT
- CARE_PROVIDER
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 187
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Time to the earlier of either radiographic progressive disease (PD) or death from any cause.
- measure
- Progression Free Survival (PFS)
- time Frame
- Up to approximately twenty months after the first subject is randomized. Time from randomization to the earlier of the following events: radiographic PD as determined by the blinded independent central review (BIRC) or death due to any cause.
- description
- Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).
- measure
- Objective Response Rate (ORR)
- time Frame
- Six months after 100 subjects are randomized. Time from randomization to best overall response of confirmed complete response (CR) or confirmed partial response (PR) per BIRC per RECIST 1.1.
Full study description
- brief Summary
- 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.
Source references
- references
- citation
- Capdevila J, Krajewska J, Hernando J, Robinson B, Sherman SI, Jarzab B, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Williamson D, Levytskyy R, Oliver J, Keam B, Brose MS. Increased Progression-Free Survival with Cabozantinib Versus Placebo in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Irrespective of Prior Vascular Endothelial Growth Factor Receptor-Targeted Therapy and Tumor Histology: A Subgroup Analysis of the COSMIC-311 Study. Thyroid. 2024 Mar;34(3):347-359. doi: 10.1089/thy.2023.0463. Epub 2024 Jan 23.
- pmid
- 38062732
- type
- DERIVED
- citation
- Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Hernando J, Faoro L, Banerjee K, Oliver JW, Keam B, Capdevila J. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1126-1138. doi: 10.1016/S1470-2045(21)00332-6. Epub 2021 Jul 5.
- pmid
- 34237250
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- igure 8: Kaplan-Meier Curve of Progression-Free Survival in CELESTIAL 14.3 Differentiated Thyroid Cancer The efficacy of CABOMETYX was evaluated in COSMIC-311 (NCT03690388), a randomized (2:1), double-blind, placebo-controlled, multicenter trial in patients with locally advanced or metastatic differentiated thyroid cancer (DTC) t
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Preserved source evidence · Not medical advice