Differentiated Thyroid CancerPhase 3NCT03690388
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
A Phase 3 study testing Cabozantinib in people with Differentiated Thyroid Cancer, run by Exelixis at 164 sites in 25 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Differentiated Thyroid Cancer
- What is being tested?
- Cabozantinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 187 participants
- Where
- 164 sitesin 25 countries
- Study dates
- 5 Oct 2018to 31 Jul 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
164 sites in 25 countries.
164 sites in 25 countries
United States31 sites
Exelixis Clinical Site #80
Ann Arbor, Michigan, 48109
Exelixis Clinical Site #9
Aurora, Colorado, 80045
Exelixis Clinical Site #5
Bethlehem, Pennsylvania, 18015
Exelixis Clinical Site #153
Boston, Massachusetts, 02114
Exelixis Clinical Site #134
Charleston, South Carolina, 29425
Exelixis Clinical Site #76
Charlotte, North Carolina, 28204
Exelixis Clinical Site #164
Chicago, Illinois, 60637
Exelixis Clinical Site #7
Cincinnati, Ohio, 45219
Exelixis Clinical Site #63
Columbia, Missouri, 65212
Exelixis Clinical Site #78
Detroit, Michigan, 48201
Exelixis Clinical Site #22
Detroit, Michigan, 48202
Exelixis Clinical Site #19
Durham, North Carolina, 27710
Exelixis Clinical Site #8
Houston, Texas, 77030
Exelixis Clinical Site #54
Lexington, Kentucky, 40536
Exelixis Clinical Site #94
Miami, Florida, 33136
Exelixis Clinical Site #118
Morristown, New Jersey, 07962
Exelixis Clinical Site #68
Nashville, Tennessee, 37232
Exelixis Clinical Site #21
New Haven, Connecticut, 06510
Exelixis Clinical Site #2
Newport Beach, California, 92658
Exelixis Clinical Site #11
Omaha, Nebraska, 68114
Exelixis Clinical Site #93
Orlando, Florida, 32804
Exelixis Clinical Site #1
Philadelphia, Pennsylvania, 19104
Exelixis Clinical Site #75
Pittsburgh, Pennsylvania, 15232
Exelixis Clinical Site #98
Sacramento, California, 95817
Exelixis Clinical Site #69
San Francisco, California, 94115
Exelixis Clinical Site #113
Seattle, Washington, 98109
Exelixis Clinical Site #42
St Louis, Missouri, 63110
Exelixis Clinical Site #10
Stanford, California, 94305
Exelixis Clinical Site #6
Tampa, Florida, 33612
Exelixis Clinical Site #3
Torrance, California, 90502
Exelixis Clinical Site #4
Washington D.C., District of Columbia, 20010
Italy16 sites
Exelixis Clinical Site #135
Catania, CT, 95122
Exelixis Clinical Site #144
Genova, GE, 16132
Exelixis Clinical Site #132
Meldola, Forlì - Cesena, 47017
Exelixis Clinical Site #103
Milan, 20133
Exelixis Clinical Site #110
Milan, 20141
Exelixis Clinical Site #115
Milan, 20149
Exelixis Clinical Site #108
Naples, 80131
Exelixis Clinical Site #56
Naples, 80131
Exelixis Clinical Site #123
Padova, 35128
Exelixis Clinical Site #29
Pisa, PI, 56124
Exelixis Clinical Site #87
Roma, 00144
Exelixis Clinical Site #127
Roma, 00161
Exelixis Clinical Site #143
Rozzano, Milano, 20089
Exelixis Clinical Site #111
Siena, 53100
Exelixis Clinical Site #120
Torino, TO, 10126
Exelixis Clinical Site #109
Viagrande, Catania, 95029
Germany12 sites
Exelixis Clinical Site #155
Aachen, 52074
Exelixis Clinical Site #131
Bonn, 53127
Exelixis Clinical Site #151
Dresden, Saxony, 01307
Exelixis Clinical Site #154
Essen, 45147
Exelixis Clinical Site #160
Freiburg im Breisgau, 79106
Exelixis Clinical Site #159
Hamburg, 20246
Exelixis Clinical Site #163
Hanover, Lower Saxony, 30625
Exelixis Clinical Site #124
Magdeburg, Saxony-Anhalt, 39120
Exelixis Clinical Site #125
Marburg, Hesse, 35043
Exelixis Clinical Site #139
München, 81377
Exelixis Clinical Site #121
Tübingen, Baden-Wurttemberg, 72076
Exelixis Clinical Site #156
Würzburg, Bavaria, 97080
Russia11 sites
Exelixis Clinical Site #55
Kislino, Kursk Oblast, 305524
Exelixis Clinical Site #49
Moscow, 117036
Exelixis Clinical Site #53
Moscow, 121309
Exelixis Clinical Site #84
Moscow, 125284
Exelixis Clinical Site #85
Moscow, 155478
Exelixis Clinical Site #48
Obninsk, Kaluzhiskiy Region, 249036
Exelixis Clinical Site #106
Omsk, 644013
Exelixis Clinical Site #89
Saint Petersburg, 198255
Exelixis Clinical Site #52
Samara, 443031
Exelixis Clinical Site #157
Tyumen, Tyumen Oblast, 625041
Exelixis Clinical Site #66
Yaroslavl, 150054
France10 sites
Exelixis Clinical Site #45
Angers, Pays de la Loire Region, 4933
Exelixis Clinical Site #102
Besançon, 25030
Exelixis Clinical Site #67
Bordeaux, New Aquitaine, 33075
Exelixis Clinical Site #32
Dijon, Bourgogne-Franche-Comté, 21079
Exelixis Clinical Site #91
Lyon, 69373
Exelixis Clinical Site #72
Marseille, Provence-Alpes-Côte d'Azur Region, 13915
Exelixis Clinical Site #82
Nice, 06189
Exelixis Clinical Site #152
Paris, 75013
Exelixis Clinical Site #95
Strasbourg, 67065
Exelixis Clinical Site #44
Villejuif, Île-de-France Region, 94805
Spain10 sites
Exelixis Clinical Site #14
Barcelona, 08035
Exelixis Clinical Site #99
Barcelona, 08036
Exelixis Clinical Site #114
Madrid, 28027
Exelixis Clinical Site #30
Madrid, 28033
Exelixis Clinical Site #13
Madrid, 28034
Exelixis Clinical Site #16
Madrid, 28040
Exelixis Clinical Site #33
Madrid, 28041
Exelixis Clinical Site #73
Madrid, 28046
Exelixis Clinical Site #23
Madrid, 28050
Exelixis Clinical Site #81
Málaga, 29010
United Kingdom9 sites
Exelixis Clinical Site #64
Aberdeen, Scotland, AB25 2ZN
Exelixis Clinical Site #88
Birmingham, England, B15 2TH
Exelixis Clinical Site #71
Bristol, England, BS2 8ED
Exelixis Clinical Site #60
Cardiff, Wales, CF14 2TL
Exelixis Clinical Site #50
Glasgow, Scotland, G12 0YN
Exelixis Clinical Site #162
London, England, SW3 6JJ
Exelixis Clinical Site #65
Manchester, M20 4BX
Exelixis Clinical Site #51
Oxford, England, OX3 7LE
Exelixis Clinical Site #57
Sheffield, S10 2SJ
Brazil8 sites
Exelixis Clinical Site #35
Cascavel, Paraná, 85806-300
Exelixis Clinical Site #39
Porto Alegre, Rio Grande do Sul, 90035-903
Exelixis Clinical Site #140
Porto Alegre, Rio Grande do Sul, 90050-170
Exelixis Clinical Site #38
Porto Alegre, Rio Grande do Sul, 90110-270
Exelixis Clinical Site #116
Ribeirão Preto, São Paulo, 14051-140
Exelixis Clinical Site #92
Rio de Janeiro, 20231-050
Exelixis Clinical Site #40
São José do Rio Preto, São Paulo, 15090-000
Exelixis Clinical Site #47
São Paulo, 01246-000
Belgium6 sites
Exelixis Clinical Site #90
Anderlecht, 1070
Exelixis Clinical Site #31
Brussels, 1200
Exelixis Clinical Site #26
Edegem, 2650
Exelixis Clinical Site #74
Edegem, 2650
Exelixis Clinical Site #100
Ghent, 9000
Exelixis Clinical Site #27
Namur, 5000
Australia5 sites
Exelixis Clinical Site #86
Bedford Park, South Australia, 5042
Exelixis Clinical Site #12
Herston, 4029
Exelixis Clinical Site #24
Melbourne, Victoria, 3004
Exelixis Clinical Site #17
St Leonards, New South Wales, 2065
Exelixis Clinical Site #25
Waratah, New South Wales, 2298
Mexico5 sites
Exelixis Clinical Site #133
Ciudad de Mèxico, 06100
Exelixis Clinical Site #147
Mexico City, 03100
Exelixis Clinical Site #148
Mexico City, 06700
Exelixis Clinical Site #161
San Luis Potosí City, 78200
Exelixis Clinical Site #158
Tuxtla Gutiérrez, Chiapas, 29038
Canada4 sites
Exelixis Clinical Site #20
Calgary, Alberta, T2N 4N2
Exelixis Clinical Site #18
Edmonton, Alberta, T6G 1Z2
Exelixis Clinical Site #107
London, Ontario, N6A 5W9
Exelixis Clinical Site #83
Toronto, Ontario, M5G 2M9
Romania4 sites
Exelixis Clinical Site #146
Bucharest, 011863
Exelixis Clinical Site #149
Cluj-Napoca, Cluj, 400015
Exelixis Clinical Site #150
Craiova, Dolj, 200385
Exelixis Clinical Site #142
Timișoara, Timiș County, 300166
South Korea4 sites
Exelixis Clinical Site #70
Busan, 49267
Exelixis Clinical Site #79
Gyeonggi-do, 10408
Exelixis Clinical Site #36
Seoul, 03080
Exelixis Clinical Site #34
Seoul, 05505
Taiwan4 sites
Exelixis Clinical Site #136
Tainan, 704
Exelixis Clinical Site #112
Tainan, 71004
Exelixis Clinical Site #77
Taipei, 10002
Exelixis Clinical Site #101
Taipei, 11490
Thailand4 sites
Exelixis Clinical Site #126
Bangkok Noi, Bangkok, 10700
Exelixis Clinical Site #130
Hat Yai, Changwat Songkhla, 90110
Exelixis Clinical Site #122
Pathum Wan, Bangkok, 10330
Exelixis Clinical Site #141
Ratchathewi, Bangkok, 10400
Argentina3 sites
Exelixis Clinical Site #97
Caba, C1012AAR
Exelixis Clinical Site #129
Córdoba, X5000AVE
Exelixis Clinical Site #96
Pergamino, Buenos Aires, B2700CPM
Croatia3 sites
Exelixis Clinical Site #145
Osijek, 31000
Exelixis Clinical Site #137
Zagreb, 10000
Exelixis Clinical Site #138
Zagreb, 10000
Israel3 sites
Exelixis Clinical Site #43
Haifa, 3109601
Exelixis Clinical Site #41
Jerusalem, 9112001
Exelixis Clinical Site #58
Petah Tikva, 4941492
Poland3 sites
Exelixis Clinical Site #61
Gliwice, Silesian Voivodeship, 44-101
Exelixis Clinical Site #59
Poznan, Greater Poland Voivodeship, 60-355
Exelixis Clinical Site #15
Warsaw, Masovian Voivodeship, 02-781
Austria2 sites
Exelixis Clinical Site #62
Salzburg, 5020
Exelixis Clinical Site #119
Vienna, 1090
Czechia2 sites
Exelixis Clinical Site #105
Brno, 656 53
Exelixis Clinical Site #104
Olomouc, 779 00
Hungary2 sites
Exelixis Clinical Site #46
Budapest, 1122
Exelixis Clinical Site #37
Pécs, 7624
Netherlands2 sites
Exelixis Clinical Site #128
Amsterdam, North Holland, 1081 HV
Exelixis Clinical Site #117
Leiden, South Holland, 2333 ZA
About this study
Official title: 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
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
- Being tested
- Cabozantinib, Placebo
- 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
- Medical subject headings
- Thyroid Cancer, Papillary, Thyroid Neoplasms, Adenocarcinoma, Follicular, Thyroid cancer, follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CabozantinibDrug
Also called XL184, Cabometyx®
Tablets containing 60-mg or 20-mg cabozantinib once daily orally.
PlaceboDrug
Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
| Study group | Role | What they receive |
|---|---|---|
| Cabozantinib | Experimental | cabozantinib (60 mg) once daily orally (qd) Receives: Drug: Cabozantinib |
| Placebo | Placebo comparator | placebo once daily orally (qd) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Time to the earlier of either radiographic progressive disease (PD) or death from any cause.
Measured: 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).
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2018
- Study start5 Oct 2018
- Primary completion19 Aug 2020
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Differentiated Thyroid CancerStudies of the same condition, open and under way.
- More trials run by ExelixisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 187 participants (actual)
Sponsor and investigators
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03690388
- Sponsor's protocol ID
- XL184-311
- Other IDs
- 2024-516478-31-00
- Status last verified
- Sep 2026
- First submitted
- 26 Sep 2018
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38062732Brose 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.
PubMed 34237250