Clinical trial NCT03690388: 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: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
Collaborators: name: Ipsen
First posted: 2018-10-01
Enrollment: 187
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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.
measure: Objective Response Rate (ORR)
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Exelixis Clinical Site #2
state: California
city: Sacramento
country: United States
facility: Exelixis Clinical Site #98
state: California
city: San Francisco
country: United States
facility: Exelixis Clinical Site #69
state: California
city: Stanford
country: United States
facility: Exelixis Clinical Site #10
state: California
city: Torrance
country: United States
facility: Exelixis Clinical Site #3
state: California
city: Aurora
country: United States
facility: Exelixis Clinical Site #9
state: Colorado
city: New Haven
country: United States
facility: Exelixis Clinical Site #21
state: Connecticut
city: Washington
country: United States
facility: Exelixis Clinical Site #4
state: District of Columbia
city: Miami
country: United States
facility: Exelixis Clinical Site #94
state: Florida
city: Orlando
country: United States
facility: Exelixis Clinical Site #93
state: Florida
city: Tampa
country: United States
facility: Exelixis Clinical Site #6
state: Florida
city: Chicago
country: United States
facility: Exelixis Clinical Site #164
state: Illinois
city: Lexington
country: United States
facility: Exelixis Clinical Site #54
state: Kentucky
city: Boston
country: United States
facility: Exelixis Clinical Site #153
state: Massachusetts
city: Ann Arbor
country: United States
facility: Exelixis Clinical Site #80
state: Michigan
city: Detroit
country: United States
facility: Exelixis Clinical Site #78
state: Michigan
city: Detroit
country: United States
facility: Exelixis Clinical Site #22
state: Michigan
city: Columbia
country: United States
facility: Exelixis Clinical Site #63
state: Missouri
city: Saint Louis
country: United States
facility: Exelixis Clinical Site #42
state: Missouri
city: Omaha
country: United States
facility: Exelixis Clinical Site #11
state: Nebraska
city: Morristown
country: United States
facility: Exelixis Clinical Site #118
state: New Jersey
city: Charlotte
country: United States
facility: Exelixis Clinical Site #76
state: North Carolina
city: Durham
country: United States
facility: Exelixis Clinical Site #19
state: North Carolina
city: Cincinnati
country: United States
facility: Exelixis Clinical Site #7
state: Ohio
city: Bethlehem
country: United States
facility: Exelixis Clinical Site #5
state: Pennsylvania
city: Philadelphia
country: United States
facility: Exelixis Clinical Site #1
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Exelixis Clinical Site #75
state: Pennsylvania
city: Charleston
country: United States
facility: Exelixis Clinical Site #134
state: South Carolina
city: Nashville
country: United States
facility: Exelixis Clinical Site #68
state: Tennessee
city: Houston
country: United States
facility: Exelixis Clinical Site #8
state: Texas
city: Seattle
country: United States
facility: Exelixis Clinical Site #113
state: Washington
city: Pergamino
country: Argentina
facility: Exelixis Clinical Site #96
state: Buenos Aires
city: Caba
country: Argentina
facility: Exelixis Clinical Site #97
city: Córdoba
country: Argentina
facility: Exelixis Clinical Site #129
city: St. Leonards
country: Australia
facility: Exelixis Clinical Site #17
state: New South Wales
city: Waratah
country: Australia
facility: Exelixis Clinical Site #25
state: New South Wales
city: Bedford Park
country: Australia
facility: Exelixis Clinical Site #86
state: South Australia
city: Melbourne
country: Australia
facility: Exelixis Clinical Site #24
state: Victoria
city: Herston
country: Australia
facility: Exelixis Clinical Site #12
city: Salzburg
country: Austria
facility: Exelixis Clinical Site #62
city: Vienna
country: Austria
facility: Exelixis Clinical Site #119
city: Anderlecht
country: Belgium
facility: Exelixis Clinical Site #90
city: Brussels
country: Belgium
facility: Exelixis Clinical Site #31
city: Edegem
country: Belgium
facility: Exelixis Clinical Site #26
city: Edegem
country: Belgium
facility: Exelixis Clinical Site #74
city: Gent
country: Belgium
facility: Exelixis Clinical Site #100
city: Namur
country: Belgium
facility: Exelixis Clinical Site #27
city: Cascavel
country: Brazil
facility: Exelixis Clinical Site #35
state: Parana
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #39
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #140
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Exelixis Clinical Site #38
state: Rio Grande Do Sul
city: Sao Jose do Rio Preto
country: Brazil
facility: Exelixis Clinical Site #40
state: Sao Paulo
city: Ribeirão Preto
country: Brazil
facility: Exelixis Clinical Site #116
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Exelixis Clinical Site #92
city: Sao Paulo
country: Brazil
facility: Exelixis Clinical Site #47
city: Calgary
country: Canada
facility: Exelixis Clinical Site #20
state: Alberta
city: Edmonton
country: Canada
facility: Exelixis Clinical Site #18
state: Alberta
city: London
country: Canada
facility: Exelixis Clinical Site #107
state: Ontario
city: Toronto
country: Canada
facility: Exelixis Clinical Site #83
state: Ontario
city: Osijek
country: Croatia
facility: Exelixis Clinical Site #145
city: Zagreb
country: Croatia
facility: Exelixis Clinical Site #137
city: Zagreb
country: Croatia
facility: Exelixis Clinical Site #138
city: Brno
country: Czechia
facility: Exelixis Clinical Site #105
city: Olomouc
country: Czechia
facility: Exelixis Clinical Site #104
city: Dijon
country: France
facility: Exelixis Clinical Site #32
state: Bourgogne-Franche-Comte
city: Villejuif
country: France
facility: Exelixis Clinical Site #44
state: Ile De France
city: Bordeaux
country: France
facility: Exelixis Clinical Site #67
state: Nouvelle - Aquitaine
city: Angers
country: France
facility: Exelixis Clinical Site #45
state: Pays De La Loire
city: Marseille
country: France
facility: Exelixis Clinical Site #72
state: Provence-Alpes-Cote d'Azur
city: Besançon
country: France
facility: Exelixis Clinical Site #102
city: Lyon Cedex 08
country: France
facility: Exelixis Clinical Site #91
city: Nice
country: France
facility: Exelixis Clinical Site #82
city: Paris
country: France
facility: Exelixis Clinical Site #152
city: Strasbourg Cedex
country: France
facility: Exelixis Clinical Site #95
city: Tübingen
country: Germany
facility: Exelixis Clinical Site #121
state: Baden-Württemberg
city: Würzburg
country: Germany
facility: Exelixis Clinical Site #156
state: Bayern
city: Marburg
country: Germany
facility: Exelixis Clinical Site #125
state: Hesse
city: Hannover
country: Germany
facility: Exelixis Clinical Site #163
state: Lower Saxony
city: Magdeburg
country: Germany
facility: Exelixis Clinical Site #124
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Exelixis Clinical Site #151
state: Saxony
city: Aachen
country: Germany
facility: Exelixis Clinical Site #155
city: Bonn
country: Germany
facility: Exelixis Clinical Site #131
city: Essen
country: Germany
facility: Exelixis Clinical Site #154
city: Freiburg
country: Germany
facility: Exelixis Clinical Site #160
city: Hamburg
country: Germany
facility: Exelixis Clinical Site #159
city: München
country: Germany
facility: Exelixis Clinical Site #139
city: Hong Kong
country: Hong Kong
facility: Exelixis Clinical Site #28
city: Budapest
country: Hungary
facility: Exelixis Clinical Site #46
city: Pecs
country: Hungary
facility: Exelixis Clinical Site #37
city: Haifa
country: Israel
facility: Exelixis Clinical Site #43
city: Jerusalem
country: Israel
facility: Exelixis Clinical Site #41
city: Petah tikva
country: Israel
facility: Exelixis Clinical Site #58
city: Viagrande
country: Italy
facility: Exelixis Clinical Site #109
state: Catania
city: Catania
country: Italy
facility: Exelixis Clinical Site #135
state: CT
city: Meldola
country: Italy
facility: Exelixis Clinical Site #132
state: Forlì - Cesena
city: Genova
country: Italy
facility: Exelixis Clinical Site #144
state: GE
city: Rozzano
country: Italy
facility: Exelixis Clinical Site #143
state: Milano
city: Pisa
country: Italy
facility: Exelixis Clinical Site #29
state: PI
city: Torino
country: Italy
facility: Exelixis Clinical Site #120
state: TO
city: Milano
country: Italy
facility: Exelixis Clinical Site #103
city: Milano
country: Italy
facility: Exelixis Clinical Site #110
city: Milano
country: Italy
facility: Exelixis Clinical Site #115
city: Napoli
country: Italy
facility: Exelixis Clinical Site #108
city: Napoli
country: Italy
facility: Exelixis Clinical Site #56
city: Padova
country: Italy
facility: Exelixis Clinical Site #123
city: Roma
country: Italy
facility: Exelixis Clinical Site #87
city: Roma
country: Italy
facility: Exelixis Clinical Site #127
city: Siena
country: Italy
facility: Exelixis Clinical Site #111
city: Busan
country: Korea, Republic of
facility: Exelixis Clinical Site #70
city: Gyeonggi-do
country: Korea, Republic of
facility: Exelixis Clinical Site #79
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #36
city: Seoul
country: Korea, Republic of
facility: Exelixis Clinical Site #34
city: Tuxtla Gutiérrez
country: Mexico
facility: Exelixis Clinical Site #158
state: Chiapas
city: Ciudad de Mèxico
country: Mexico
facility: Exelixis Clinical Site #133
city: Ciudad de México
country: Mexico
facility: Exelixis Clinical Site #147
city: Ciudad de México
country: Mexico
facility: Exelixis Clinical Site #148
city: San Luis Potosí
country: Mexico
facility: Exelixis Clinical Site #161
city: Amsterdam
country: Netherlands
facility: Exelixis Clinical Site #128
state: Noord-Holland
city: Leiden
country: Netherlands
facility: Exelixis Clinical Site #117
state: Zuid-Holland
city: Warszawa
country: Poland
facility: Exelixis Clinical Site #15
state: Mazowieckie
city: Gliwice
country: Poland
facility: Exelixis Clinical Site #61
state: Slaskie
city: Poznan
country: Poland
facility: Exelixis Clinical Site #59
state: Wielkopolskie
city: Cluj-Napoca
country: Romania
facility: Exelixis Clinical Site #149
state: Cluj
city: Craiova
country: Romania
facility: Exelixis Clinical Site #150
state: Dolj
city: Timişoara
country: Romania
facility: Exelixis Clinical Site #142
state: Timis
city: Bucuresti
country: Romania
facility: Exelixis Clinical Site #146
city: Obninsk
country: Russian Federation
facility: Exelixis Clinical Site #48
state: Kaluzhiskiy Region
city: Kislino
country: Russian Federation
facility: Exelixis Clinical Site #55
state: Kursk Region
city: Tyumen
country: Russian Federation
facility: Exelixis Clinical Site #157
state: Tyumen Region
city: Moscow
country: Russian Federation
facility: Exelixis Clinical Site #49
city: Moscow
country: Russian Federation
facility: Exelixis Clinical Site #53
city: Moscow
country: Russian Federation
facility: Exelixis Clinical Site #84
city: Moscow
country: Russian Federation
facility: Exelixis Clinical Site #85
city: Omsk
country: Russian Federation
facility: Exelixis Clinical Site #106
city: Saint Petersburg
country: Russian Federation
facility: Exelixis Clinical Site #89
city: Samara
country: Russian Federation
facility: Exelixis Clinical Site #52
city: Yaroslavl
country: Russian Federation
facility: Exelixis Clinical Site #66
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #14
city: Barcelona
country: Spain
facility: Exelixis Clinical Site #99
city: Madrid
country: Spain
facility: Exelixis Clinical Site #114
city: Madrid
country: Spain
facility: Exelixis Clinical Site #30
city: Madrid
country: Spain
facility: Exelixis Clinical Site #13
city: Madrid
country: Spain
facility: Exelixis Clinical Site #16
city: Madrid
country: Spain
facility: Exelixis Clinical Site #33
city: Madrid
country: Spain
facility: Exelixis Clinical Site #73
city: Madrid
country: Spain
facility: Exelixis Clinical Site #23
city: Málaga
country: Spain
facility: Exelixis Clinical Site #81
city: Tainan
country: Taiwan
facility: Exelixis Clinical Site #136
city: Tainan
country: Taiwan
facility: Exelixis Clinical Site #112
city: Taipei
country: Taiwan
facility: Exelixis Clinical Site #77
city: Taipei
country: Taiwan
facility: Exelixis Clinical Site #101
city: Bangkok Noi
country: Thailand
facility: Exelixis Clinical Site #126
state: Bangkok
city: Pathum Wan
country: Thailand
facility: Exelixis Clinical Site #122
state: Bangkok
city: Ratchathewi
country: Thailand
facility: Exelixis Clinical Site #141
state: Bangkok
city: Hat Yai
country: Thailand
facility: Exelixis Clinical Site #130
state: Songkla
city: Birmingham
country: United Kingdom
facility: Exelixis Clinical Site #88
state: England
city: Bristol
country: United Kingdom
facility: Exelixis Clinical Site #71
state: England
city: London
country: United Kingdom
facility: Exelixis Clinical Site #162
state: England
city: Oxford
country: United Kingdom
facility: Exelixis Clinical Site #51
state: England
city: Aberdeen
country: United Kingdom
facility: Exelixis Clinical Site #64
state: Scotland
city: Glasgow
country: United Kingdom
facility: Exelixis Clinical Site #50
state: Scotland
city: Cardiff
country: United Kingdom
facility: Exelixis Clinical Site #60
state: Wales
city: Manchester
country: United Kingdom
facility: Exelixis Clinical Site #65
city: Sheffield
country: United Kingdom
facility: Exelixis Clinical Site #57
Study officials:
References:
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.