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

NCT ID: NCT03690388

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-05
• Study Completion Date: 2026-07-31

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.

Conditions

Differentiated Thyroid Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Cabozantinib

cabozantinib (60 mg) once daily orally (qd)

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Tablets containing 60-mg or 20-mg cabozantinib once daily orally.

Placebo

placebo once daily orally (qd)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.

Interventions

Cabozantinib

Tablets containing 60-mg or 20-mg cabozantinib once daily orally.

Intervention Type: DRUG

Placebo

Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.

Intervention Type: DRUG

Other Intervention Names

XL184; Cabometyx®

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: collaborator

Exelixis

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Exelixis Clinical Site #2

Newport Beach, California, United States

Exelixis Clinical Site #98

Sacramento, California, United States

Exelixis Clinical Site #69

San Francisco, California, United States

Exelixis Clinical Site #10

Stanford, California, United States

Exelixis Clinical Site #3

Torrance, California, United States

Exelixis Clinical Site #9

Aurora, Colorado, United States

Exelixis Clinical Site #21

New Haven, Connecticut, United States

Exelixis Clinical Site #4

Washington D.C., District of Columbia, United States

Exelixis Clinical Site #94

Miami, Florida, United States

Exelixis Clinical Site #93

Orlando, Florida, United States

Exelixis Clinical Site #6

Tampa, Florida, United States

Exelixis Clinical Site #164

Chicago, Illinois, United States

Exelixis Clinical Site #54

Lexington, Kentucky, United States

Exelixis Clinical Site #153

Boston, Massachusetts, United States

Exelixis Clinical Site #80

Ann Arbor, Michigan, United States

Exelixis Clinical Site #78

Detroit, Michigan, United States

Exelixis Clinical Site #22

Detroit, Michigan, United States

Exelixis Clinical Site #63

Columbia, Missouri, United States

Exelixis Clinical Site #42

St Louis, Missouri, United States

Exelixis Clinical Site #11

Omaha, Nebraska, United States

Exelixis Clinical Site #118

Morristown, New Jersey, United States

Exelixis Clinical Site #76

Charlotte, North Carolina, United States

Exelixis Clinical Site #19

Durham, North Carolina, United States

Exelixis Clinical Site #7

Cincinnati, Ohio, United States

Exelixis Clinical Site #5

Bethlehem, Pennsylvania, United States

Exelixis Clinical Site #1

Philadelphia, Pennsylvania, United States

Exelixis Clinical Site #75

Pittsburgh, Pennsylvania, United States

Exelixis Clinical Site #134

Charleston, South Carolina, United States

Exelixis Clinical Site #68

Nashville, Tennessee, United States

Exelixis Clinical Site #8

Houston, Texas, United States

Exelixis Clinical Site #113

Seattle, Washington, United States

Exelixis Clinical Site #96

Pergamino, Buenos Aires, Argentina

Exelixis Clinical Site #97

Caba, , Argentina

Exelixis Clinical Site #129

Córdoba, , Argentina

Exelixis Clinical Site #17

St Leonards, New South Wales, Australia

Exelixis Clinical Site #25

Waratah, New South Wales, Australia

Exelixis Clinical Site #86

Bedford Park, South Australia, Australia

Exelixis Clinical Site #24

Melbourne, Victoria, Australia

Exelixis Clinical Site #12

Herston, , Australia

Exelixis Clinical Site #62

Salzburg, , Austria

Exelixis Clinical Site #119

Vienna, , Austria

Exelixis Clinical Site #90

Anderlecht, , Belgium

Exelixis Clinical Site #31

Brussels, , Belgium

Exelixis Clinical Site #26

Edegem, , Belgium

Exelixis Clinical Site #74

Edegem, , Belgium

Exelixis Clinical Site #100

Ghent, , Belgium

Exelixis Clinical Site #27

Namur, , Belgium

Exelixis Clinical Site #35

Cascavel, Paraná, Brazil

Exelixis Clinical Site #39

Porto Alegre, Rio Grande do Sul, Brazil

Exelixis Clinical Site #140

Porto Alegre, Rio Grande do Sul, Brazil

Exelixis Clinical Site #38

Porto Alegre, Rio Grande do Sul, Brazil

Exelixis Clinical Site #116

Ribeirão Preto, São Paulo, Brazil

Exelixis Clinical Site #40

São José do Rio Preto, São Paulo, Brazil

Exelixis Clinical Site #92

Rio de Janeiro, , Brazil

Exelixis Clinical Site #47

São Paulo, , Brazil

Exelixis Clinical Site #20

Calgary, Alberta, Canada

Exelixis Clinical Site #18

Edmonton, Alberta, Canada

Exelixis Clinical Site #107

London, Ontario, Canada

Exelixis Clinical Site #83

Toronto, Ontario, Canada

Exelixis Clinical Site #145

Osijek, , Croatia

Exelixis Clinical Site #137

Zagreb, , Croatia

Exelixis Clinical Site #138

Zagreb, , Croatia

Exelixis Clinical Site #105

Brno, , Czechia

Exelixis Clinical Site #104

Olomouc, , Czechia

Exelixis Clinical Site #32

Dijon, Bourgogne-Franche-Comté, France

Exelixis Clinical Site #67

Bordeaux, Nouvelle-Aquitaine, France

Exelixis Clinical Site #45

Angers, Pays de la Loire Region, France

Exelixis Clinical Site #72

Marseille, Provence-Alpes-Côte d'Azur Region, France

Exelixis Clinical Site #102

Besançon, , France

Exelixis Clinical Site #91

Lyon, , France

Exelixis Clinical Site #82

Nice, , France

Exelixis Clinical Site #152

Paris, , France

Exelixis Clinical Site #95

Strasbourg, , France

Exelixis Clinical Site #44

Villejuif, Île-de-France Region, France

Exelixis Clinical Site #121

Tübingen, Baden-Wurttemberg, Germany

Exelixis Clinical Site #156

Würzburg, Bavaria, Germany

Exelixis Clinical Site #125

Marburg, Hesse, Germany

Exelixis Clinical Site #163

Hanover, Lower Saxony, Germany

Exelixis Clinical Site #151

Dresden, Saxony, Germany

Exelixis Clinical Site #124

Magdeburg, Saxony-Anhalt, Germany

Exelixis Clinical Site #155

Aachen, , Germany

Exelixis Clinical Site #131

Bonn, , Germany

Exelixis Clinical Site #154

Essen, , Germany

Exelixis Clinical Site #160

Freiburg im Breisgau, , Germany

Exelixis Clinical Site #159

Hamburg, , Germany

Exelixis Clinical Site #139

München, , Germany

Exelixis Clinical Site #28

Hong Kong, , Hong Kong

Exelixis Clinical Site #46

Budapest, , Hungary

Exelixis Clinical Site #37

Pécs, , Hungary

Exelixis Clinical Site #43

Haifa, , Israel

Exelixis Clinical Site #41

Jerusalem, , Israel

Exelixis Clinical Site #58

Petah Tikva, , Israel

Exelixis Clinical Site #109

Viagrande, Catania, Italy

Exelixis Clinical Site #135

Catania, CT, Italy

Exelixis Clinical Site #132

Meldola, Forlì - Cesena, Italy

Exelixis Clinical Site #144

Genova, GE, Italy

Exelixis Clinical Site #143

Rozzano, Milano, Italy

Exelixis Clinical Site #29

Pisa, PI, Italy

Exelixis Clinical Site #120

Torino, TO, Italy

Exelixis Clinical Site #103

Milan, , Italy

Exelixis Clinical Site #110

Milan, , Italy

Exelixis Clinical Site #115

Milan, , Italy

Exelixis Clinical Site #108

Napoli, , Italy

Exelixis Clinical Site #56

Napoli, , Italy

Exelixis Clinical Site #123

Padua, , Italy

Exelixis Clinical Site #87

Roma, , Italy

Exelixis Clinical Site #127

Roma, , Italy

Exelixis Clinical Site #111

Siena, , Italy

Exelixis Clinical Site #158

Tuxtla Gutiérrez, Chiapas, Mexico

Exelixis Clinical Site #133

Ciudad de Mèxico, , Mexico

Exelixis Clinical Site #147

Mexico City, , Mexico

Exelixis Clinical Site #148

Mexico City, , Mexico

Exelixis Clinical Site #161

San Luis Potosí City, , Mexico

Exelixis Clinical Site #128

Amsterdam, North Holland, Netherlands

Exelixis Clinical Site #117

Leiden, South Holland, Netherlands

Exelixis Clinical Site #59

Poznan, Greater Poland Voivodeship, Poland

Exelixis Clinical Site #15

Warsaw, Masovian Voivodeship, Poland

Exelixis Clinical Site #61

Gliwice, Silesian Voivodeship, Poland

Exelixis Clinical Site #149

Cluj-Napoca, Cluj, Romania

Exelixis Clinical Site #150

Craiova, Dolj, Romania

Exelixis Clinical Site #142

Timișoara, Timiș County, Romania

Exelixis Clinical Site #146

Bucharest, , Romania

Exelixis Clinical Site #48

Obninsk, Kaluzhiskiy Region, Russia

Exelixis Clinical Site #55

Kislino, Kursk Oblast, Russia

Exelixis Clinical Site #157

Tyumen, Tyumen Oblast, Russia

Exelixis Clinical Site #49

Moscow, , Russia

Exelixis Clinical Site #53

Moscow, , Russia

Exelixis Clinical Site #84

Moscow, , Russia

Exelixis Clinical Site #85

Moscow, , Russia

Exelixis Clinical Site #106

Omsk, , Russia

Exelixis Clinical Site #89

Saint Petersburg, , Russia

Exelixis Clinical Site #52

Samara, , Russia

Exelixis Clinical Site #66

Yaroslavl, , Russia

Exelixis Clinical Site #70

Busan, , South Korea

Exelixis Clinical Site #79

Gyeonggi-do, , South Korea

Exelixis Clinical Site #36

Seoul, , South Korea

Exelixis Clinical Site #34

Seoul, , South Korea

Exelixis Clinical Site #14

Barcelona, , Spain

Exelixis Clinical Site #99

Barcelona, , Spain

Exelixis Clinical Site #114

Madrid, , Spain

Exelixis Clinical Site #30

Madrid, , Spain

Exelixis Clinical Site #13

Madrid, , Spain

Exelixis Clinical Site #16

Madrid, , Spain

Exelixis Clinical Site #33

Madrid, , Spain

Exelixis Clinical Site #73

Madrid, , Spain

Exelixis Clinical Site #23

Madrid, , Spain

Exelixis Clinical Site #81

Málaga, , Spain

Exelixis Clinical Site #136

Tainan City, , Taiwan

Exelixis Clinical Site #112

Tainan City, , Taiwan

Exelixis Clinical Site #77

Taipei, , Taiwan

Exelixis Clinical Site #101

Taipei, , Taiwan

Exelixis Clinical Site #126

Bangkok Noi, Bangkok, Thailand

Exelixis Clinical Site #122

Pathum Wan, Bangkok, Thailand

Exelixis Clinical Site #141

Ratchathewi, Bangkok, Thailand

Exelixis Clinical Site #130

Hat Yai, Changwat Songkhla, Thailand

Exelixis Clinical Site #88

Birmingham, England, United Kingdom

Exelixis Clinical Site #71

Bristol, England, United Kingdom

Exelixis Clinical Site #162

London, England, United Kingdom

Exelixis Clinical Site #51

Oxford, England, United Kingdom

Exelixis Clinical Site #64

Aberdeen, Scotland, United Kingdom

Exelixis Clinical Site #50

Glasgow, Scotland, United Kingdom

Exelixis Clinical Site #60

Cardiff, Wales, United Kingdom

Exelixis Clinical Site #65

Manchester, , United Kingdom

Exelixis Clinical Site #57

Sheffield, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Croatia; Czechia; France; Germany; Hong Kong; Hungary; Israel; Italy; Mexico; Netherlands; Poland; Romania; Russia; South Korea; Spain; Taiwan; Thailand; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38062732 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34237250 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2024-516478-31-00

Identifier Type: CTIS

Identifier Source: secondary_id

XL184-311

Identifier Type: -

Identifier Source: org_study_id