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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

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ClinicalTrials.gov Identifier: NCT03690388
Recruitment Status : Active, not recruiting
First Posted : October 1, 2018
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
Exelixis

Tracking Information
First Submitted Date  ICMJE September 26, 2018
First Posted Date  ICMJE October 1, 2018
Last Update Posted Date July 15, 2021
Actual Study Start Date  ICMJE October 5, 2018
Actual Primary Completion Date August 19, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2021)
  • 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. ]
    Time to the earlier of either radiographic progressive disease (PD) or death from any cause.
  • 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. ]
    Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).
Original Primary Outcome Measures  ICMJE
 (submitted: September 27, 2018)
  • 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 BIRC or death due to any cause. ]
    Time to the earlier of either radiographic PD or death from any cause.
  • Objective Response Rate (ORR) [ Time Frame: Six months after 100 subjects are randomized. Time from randomization to best overall response of confirmed CR or confirmed PR per BIRC per RECIST 1.1. ]
    Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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: Triple (Participant, Care Provider, Investigator)
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).
Primary Purpose: Treatment
Condition  ICMJE Differentiated Thyroid Cancer
Intervention  ICMJE
  • Drug: Cabozantinib
    Tablets containing 60-mg or 20-mg cabozantinib once daily orally.
    Other Names:
    • XL184
    • Cabometyx®
  • Drug: Placebo
    Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Study Arms  ICMJE
  • Experimental: Cabozantinib
    cabozantinib (60 mg) once daily orally (qd)
    Intervention: Drug: Cabozantinib
  • Placebo Comparator: Placebo
    placebo once daily orally (qd)
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 2, 2021)
258
Original Estimated Enrollment  ICMJE
 (submitted: September 27, 2018)
300
Estimated Study Completion Date  ICMJE December 2022
Actual Primary Completion Date August 19, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Croatia,   Czechia,   France,   Germany,   Hong Kong,   Hungary,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Romania,   Russian Federation,   Spain,   Taiwan,   Thailand,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03690388
Other Study ID Numbers  ICMJE XL184-311
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Exelixis
Study Sponsor  ICMJE Exelixis
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Exelixis
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP