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

NCT03690388 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: XL184-3112024-516478-31-00
• Study Type: interventional
• Target: 187
• Locations: 24 countries
• Sites: 162

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

Keywords

Thyroid cancer, papillary; Papillary thyroid carcinoma; Nonmedullary thyroid carcinoma; Cancer of the thyroid; Thyroid cancer; Follicular thyroid cancer; Thyroid cancer, follicular; Hürthle cell cancer

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  Time to the earlier of either radiographic progressive disease (PD) or death from any cause.

  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.

• Objective Response Rate (ORR)

  Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).

  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.

Study Arms (2)

Cabozantinib

EXPERIMENTAL

cabozantinib (60 mg) once daily orally (qd)

Drug: Cabozantinib

Placebo

PLACEBO COMPARATOR

placebo once daily orally (qd)

Drug: Placebo

Interventions

Cabozantinib DRUG

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

Also known as: XL184, Cabometyx®

Cabozantinib

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of Differentiated Thyroid Cancer (DTC)
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Previously treated with or deemed ineligible for treatment with Iodine- 131 for differentiated thyroid cancer (DTC)
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

You may not qualify if:

• 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)
• 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
• Receipt of any type of anticancer antibody (including investigational antibody) or systemic chemotherapy within 4 weeks before randomization
• Receipt of radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before randomization.
• Known brain metastases or cranial epidural disease unless adequately treated

Sponsors & Collaborators

• Exelixis: lead
• Ipsen: collaborator

Study Sites (164)

Exelixis Clinical Site #2

Newport Beach, California, 92658, United States

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Exelixis Clinical Site #98

Sacramento, California, 95817, United States

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Exelixis Clinical Site #69

San Francisco, California, 94115, United States

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Exelixis Clinical Site #10

Stanford, California, 94305, United States

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Exelixis Clinical Site #3

Torrance, California, 90502, United States

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Exelixis Clinical Site #9

Aurora, Colorado, 80045, United States

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Exelixis Clinical Site #21

New Haven, Connecticut, 06510, United States

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Exelixis Clinical Site #4

Washington D.C., District of Columbia, 20010, United States

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Exelixis Clinical Site #94

Miami, Florida, 33136, United States

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Exelixis Clinical Site #93

Orlando, Florida, 32804, United States

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Exelixis Clinical Site #6

Tampa, Florida, 33612, United States

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Exelixis Clinical Site #164

Chicago, Illinois, 60637, United States

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Exelixis Clinical Site #54

Lexington, Kentucky, 40536, United States

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Exelixis Clinical Site #153

Boston, Massachusetts, 02114, United States

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Exelixis Clinical Site #80

Ann Arbor, Michigan, 48109, United States

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Exelixis Clinical Site #78

Detroit, Michigan, 48201, United States

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Exelixis Clinical Site #22

Detroit, Michigan, 48202, United States

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Exelixis Clinical Site #63

Columbia, Missouri, 65212, United States

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Exelixis Clinical Site #42

St Louis, Missouri, 63110, United States

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Exelixis Clinical Site #11

Omaha, Nebraska, 68114, United States

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Exelixis Clinical Site #118

Morristown, New Jersey, 07962, United States

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Exelixis Clinical Site #76

Charlotte, North Carolina, 28204, United States

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Exelixis Clinical Site #19

Durham, North Carolina, 27710, United States

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Exelixis Clinical Site #7

Cincinnati, Ohio, 45219, United States

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Exelixis Clinical Site #5

Bethlehem, Pennsylvania, 18015, United States

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Exelixis Clinical Site #1

Philadelphia, Pennsylvania, 19104, United States

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Exelixis Clinical Site #75

Pittsburgh, Pennsylvania, 15232, United States

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Exelixis Clinical Site #134

Charleston, South Carolina, 29425, United States

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Exelixis Clinical Site #68

Nashville, Tennessee, 37232, United States

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Exelixis Clinical Site #8

Houston, Texas, 77030, United States

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Exelixis Clinical Site #113

Seattle, Washington, 98109, United States

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Exelixis Clinical Site #96

Pergamino, Buenos Aires, B2700CPM, Argentina

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Exelixis Clinical Site #97

Caba, C1012AAR, Argentina

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Exelixis Clinical Site #129

Córdoba, X5000AVE, Argentina

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Exelixis Clinical Site #17

St Leonards, New South Wales, 2065, Australia

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Exelixis Clinical Site #25

Waratah, New South Wales, 2298, Australia

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Exelixis Clinical Site #86

Bedford Park, South Australia, 5042, Australia

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Exelixis Clinical Site #24

Melbourne, Victoria, 3004, Australia

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Exelixis Clinical Site #12

Herston, 4029, Australia

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Exelixis Clinical Site #62

Salzburg, 5020, Austria

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Exelixis Clinical Site #119

Vienna, 1090, Austria

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Exelixis Clinical Site #90

Anderlecht, 1070, Belgium

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Exelixis Clinical Site #31

Brussels, 1200, Belgium

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Exelixis Clinical Site #26

Edegem, 2650, Belgium

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Exelixis Clinical Site #74

Edegem, 2650, Belgium

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Exelixis Clinical Site #100

Ghent, 9000, Belgium

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Exelixis Clinical Site #27

Namur, 5000, Belgium

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Exelixis Clinical Site #35

Cascavel, Paraná, 85806-300, Brazil

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Exelixis Clinical Site #39

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

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Exelixis Clinical Site #140

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

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Exelixis Clinical Site #38

Porto Alegre, Rio Grande do Sul, 90110-270, Brazil

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Exelixis Clinical Site #116

Ribeirão Preto, São Paulo, 14051-140, Brazil

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Exelixis Clinical Site #40

São José do Rio Preto, São Paulo, 15090-000, Brazil

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Exelixis Clinical Site #92

Rio de Janeiro, 20231-050, Brazil

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Exelixis Clinical Site #47

São Paulo, 01246-000, Brazil

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Exelixis Clinical Site #20

Calgary, Alberta, T2N 4N2, Canada

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Exelixis Clinical Site #18

Edmonton, Alberta, T6G 1Z2, Canada

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Exelixis Clinical Site #107

London, Ontario, N6A 5W9, Canada

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Exelixis Clinical Site #83

Toronto, Ontario, M5G 2M9, Canada

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Exelixis Clinical Site #145

Osijek, 31000, Croatia

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Exelixis Clinical Site #137

Zagreb, 10000, Croatia

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Exelixis Clinical Site #138

Zagreb, 10000, Croatia

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Exelixis Clinical Site #105

Brno, 656 53, Czechia

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Exelixis Clinical Site #104

Olomouc, 779 00, Czechia

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Exelixis Clinical Site #32

Dijon, Bourgogne-Franche-Comté, 21079, France

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Exelixis Clinical Site #67

Bordeaux, Nouvelle-Aquitaine, 33075, France

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Exelixis Clinical Site #45

Angers, Pays de la Loire Region, 4933, France

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Exelixis Clinical Site #72

Marseille, Provence-Alpes-Côte d'Azur Region, 13915, France

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Exelixis Clinical Site #102

Besançon, 25030, France

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Exelixis Clinical Site #91

Lyon, 69373, France

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Exelixis Clinical Site #82

Nice, 06189, France

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Exelixis Clinical Site #152

Paris, 75013, France

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Exelixis Clinical Site #95

Strasbourg, 67065, France

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Exelixis Clinical Site #44

Villejuif, Île-de-France Region, 94805, France

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Exelixis Clinical Site #121

Tübingen, Baden-Wurttemberg, 72076, Germany

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Exelixis Clinical Site #156

Würzburg, Bavaria, 97080, Germany

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Exelixis Clinical Site #125

Marburg, Hesse, 35043, Germany

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Exelixis Clinical Site #163

Hanover, Lower Saxony, 30625, Germany

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Exelixis Clinical Site #151

Dresden, Saxony, 01307, Germany

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Exelixis Clinical Site #124

Magdeburg, Saxony-Anhalt, 39120, Germany

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Exelixis Clinical Site #155

Aachen, 52074, Germany

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Exelixis Clinical Site #131

Bonn, 53127, Germany

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Exelixis Clinical Site #154

Essen, 45147, Germany

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Exelixis Clinical Site #160

Freiburg im Breisgau, 79106, Germany

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Exelixis Clinical Site #159

Hamburg, 20246, Germany

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Exelixis Clinical Site #139

München, 81377, Germany

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Exelixis Clinical Site #28

Hong Kong, Hong Kong

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Exelixis Clinical Site #46

Budapest, 1122, Hungary

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Exelixis Clinical Site #37

Pécs, 7624, Hungary

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Exelixis Clinical Site #43

Haifa, 3109601, Israel

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Exelixis Clinical Site #41

Jerusalem, 9112001, Israel

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Exelixis Clinical Site #58

Petah Tikva, 4941492, Israel

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Exelixis Clinical Site #109

Viagrande, Catania, 95029, Italy

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Exelixis Clinical Site #135

Catania, CT, 95122, Italy

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Exelixis Clinical Site #132

Meldola, Forlì - Cesena, 47017, Italy

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Exelixis Clinical Site #144

Genova, GE, 16132, Italy

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Exelixis Clinical Site #143

Rozzano, Milano, 20089, Italy

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Exelixis Clinical Site #29

Pisa, PI, 56124, Italy

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Exelixis Clinical Site #120

Torino, TO, 10126, Italy

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Exelixis Clinical Site #103

Milan, 20133, Italy

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Exelixis Clinical Site #110

Milan, 20141, Italy

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Exelixis Clinical Site #115

Milan, 20149, Italy

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Exelixis Clinical Site #108

Napoli, 80131, Italy

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Exelixis Clinical Site #56

Napoli, 80131, Italy

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Exelixis Clinical Site #123

Padua, 35128, Italy

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Exelixis Clinical Site #87

Roma, 00144, Italy

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Exelixis Clinical Site #127

Roma, 00161, Italy

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Exelixis Clinical Site #111

Siena, 53100, Italy

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Exelixis Clinical Site #158

Tuxtla Gutiérrez, Chiapas, 29038, Mexico

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Exelixis Clinical Site #133

Ciudad de Mèxico, 06100, Mexico

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Exelixis Clinical Site #147

Mexico City, 03100, Mexico

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Exelixis Clinical Site #148

Mexico City, 06700, Mexico

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Exelixis Clinical Site #161

San Luis Potosí City, 78200, Mexico

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Exelixis Clinical Site #128

Amsterdam, North Holland, 1081 HV, Netherlands

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Exelixis Clinical Site #117

Leiden, South Holland, 2333 ZA, Netherlands

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Exelixis Clinical Site #59

Poznan, Greater Poland Voivodeship, 60-355, Poland

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Exelixis Clinical Site #15

Warsaw, Masovian Voivodeship, 02-781, Poland

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Exelixis Clinical Site #61

Gliwice, Silesian Voivodeship, 44-101, Poland

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Exelixis Clinical Site #149

Cluj-Napoca, Cluj, 400015, Romania

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Exelixis Clinical Site #150

Craiova, Dolj, 200385, Romania

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Exelixis Clinical Site #142

Timișoara, Timiș County, 300166, Romania

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Exelixis Clinical Site #146

Bucharest, 011863, Romania

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Exelixis Clinical Site #48

Obninsk, Kaluzhiskiy Region, 249036, Russia

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Exelixis Clinical Site #55

Kislino, Kursk Oblast, 305524, Russia

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Exelixis Clinical Site #157

Tyumen, Tyumen Oblast, 625041, Russia

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Exelixis Clinical Site #49

Moscow, 117036, Russia

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Exelixis Clinical Site #53

Moscow, 121309, Russia

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Exelixis Clinical Site #84

Moscow, 125284, Russia

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Exelixis Clinical Site #85

Moscow, 155478, Russia

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Exelixis Clinical Site #106

Omsk, 644013, Russia

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Exelixis Clinical Site #89

Saint Petersburg, 198255, Russia

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Exelixis Clinical Site #52

Samara, 443031, Russia

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Exelixis Clinical Site #66

Yaroslavl, 150054, Russia

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Exelixis Clinical Site #70

Busan, 49267, South Korea

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Exelixis Clinical Site #79

Gyeonggi-do, 10408, South Korea

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Exelixis Clinical Site #36

Seoul, 03080, South Korea

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Exelixis Clinical Site #34

Seoul, 05505, South Korea

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Exelixis Clinical Site #14

Barcelona, 08035, Spain

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Exelixis Clinical Site #99

Barcelona, 08036, Spain

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Exelixis Clinical Site #114

Madrid, 28027, Spain

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Exelixis Clinical Site #30

Madrid, 28033, Spain

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Exelixis Clinical Site #13

Madrid, 28034, Spain

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Exelixis Clinical Site #16

Madrid, 28040, Spain

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Exelixis Clinical Site #33

Madrid, 28041, Spain

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Exelixis Clinical Site #73

Madrid, 28046, Spain

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Exelixis Clinical Site #23

Madrid, 28050, Spain

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Exelixis Clinical Site #81

Málaga, 29010, Spain

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Exelixis Clinical Site #136

Tainan, 704, Taiwan

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Exelixis Clinical Site #112

Tainan, 71004, Taiwan

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Exelixis Clinical Site #77

Taipei, 10002, Taiwan

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Exelixis Clinical Site #101

Taipei, 11490, Taiwan

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Exelixis Clinical Site #126

Bangkok Noi, Bangkok, 10700, Thailand

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Exelixis Clinical Site #122

Pathum Wan, Bangkok, 10330, Thailand

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Exelixis Clinical Site #141

Ratchathewi, Bangkok, 10400, Thailand

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Exelixis Clinical Site #130

Hat Yai, Changwat Songkhla, 90110, Thailand

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Exelixis Clinical Site #88

Birmingham, England, B15 2TH, United Kingdom

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Exelixis Clinical Site #71

Bristol, England, BS2 8ED, United Kingdom

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Exelixis Clinical Site #162

London, England, SW3 6JJ, United Kingdom

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Exelixis Clinical Site #51

Oxford, England, OX3 7LE, United Kingdom

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Exelixis Clinical Site #64

Aberdeen, Scotland, AB25 2ZN, United Kingdom

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Exelixis Clinical Site #50

Glasgow, Scotland, G12 0YN, United Kingdom

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Exelixis Clinical Site #60

Cardiff, Wales, CF14 2TL, United Kingdom

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Exelixis Clinical Site #65

Manchester, M20 4BX, United Kingdom

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Exelixis Clinical Site #57

Sheffield, S10 2SJ, United Kingdom

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Related Publications (2)

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Thyroid Cancer, Papillary; Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid cancer, follicular

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc.

druginfo@exelixis.com

855-292-3935

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: October 1, 2018
• Study Start: October 5, 2018
• Primary Completion: August 19, 2020
• Study Completion (Estimated): July 31, 2026
• Last Updated: September 25, 2025
• Results First Posted: May 18, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); ES (10); FR (10); IL (3); CZ (2); ME (5); PL (3); RU (11); BR (8); CR (3); HK (1); BE (6); HU (2); CA (4); AR (3); NL (2); RO (4); US (31); KR (4); DE (12); TW (4); IT (16); TH (4); GB (9)