Study 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
Submitted Date:  November 10, 2021 (v33)
Quality Control Review Has Not Concluded

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Open or close this module Study Identification
Unique Protocol ID: XL184-311
Brief Title: 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
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2021
Overall Status: Active, not recruiting
Study Start: October 5, 2018
Primary Completion: August 19, 2020 [Actual]
Study Completion: December 2022 [Anticipated]
First Submitted: September 26, 2018
First Submitted that
Met QC Criteria:
September 27, 2018
First Posted: October 1, 2018 [Actual]
Results First Submitted: November 10, 2021
Results First Submitted that
Met QC Criteria:
Results First Posted: December 9, 2021 [Actual]
Certification/Extension
First Submitted:
May 5, 2021
Certification/Extension
First Submitted that
Met QC Criteria:
June 2, 2021
Certification/Extension
First Posted:
June 10, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: December 9, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Exelixis
Responsible Party: Sponsor
Collaborators: Ipsen
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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:
Open or close this module Conditions
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
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
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.
Number of Arms: 2
Masking: Triple (Participant, Care Provider, Investigator)
Allocation: Randomized
Enrollment: 187 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cabozantinib
cabozantinib (60 mg) once daily orally (qd)
Drug: Cabozantinib
Tablets containing 60-mg or 20-mg cabozantinib once daily orally.
Other Names:
  • XL184
  • Cabometyx®
Placebo Comparator: Placebo
placebo once daily orally (qd)
Drug: Placebo
Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. 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.
2. 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).
Open or close this module Eligibility
Minimum Age: 16 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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
Open or close this module Contacts/Locations
Locations: United States, California
Exelixis Clinical Site #2
Newport Beach, California, United States, 92658
Exelixis Clinical Site #98
Sacramento, California, United States, 95817
Exelixis Clinical Site #69
San Francisco, California, United States, 94115
Exelixis Clinical Site #10
Stanford, California, United States, 94305
Exelixis Clinical Site #3
Torrance, California, United States, 90502
United States, Colorado
Exelixis Clinical Site #9
Aurora, Colorado, United States, 80045
United States, Connecticut
Exelixis Clinical Site #21
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Exelixis Clinical Site #4
Washington, District of Columbia, United States, 20010
United States, Florida
Exelixis Clinical Site #94
Miami, Florida, United States, 33136
Exelixis Clinical Site #93
Orlando, Florida, United States, 32804
Exelixis Clinical Site #6
Tampa, Florida, United States, 33612
United States, Illinois
Exelixis Clinical Site #164
Chicago, Illinois, United States, 60637
United States, Kentucky
Exelixis Clinical Site #54
Lexington, Kentucky, United States, 40536
United States, Massachusetts
Exelixis Clinical Site #153
Boston, Massachusetts, United States, 02114
United States, Michigan
Exelixis Clinical Site #80
Ann Arbor, Michigan, United States, 48109
Exelixis Clinical Site #78
Detroit, Michigan, United States, 48201
Exelixis Clinical Site #22
Detroit, Michigan, United States, 48202
United States, Missouri
Exelixis Clinical Site #63
Columbia, Missouri, United States, 65212
Exelixis Clinical Site #42
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Exelixis Clinical Site #11
Omaha, Nebraska, United States, 68114
United States, New Jersey
Exelixis Clinical Site #118
Morristown, New Jersey, United States, 07962
United States, North Carolina
Exelixis Clinical Site #76
Charlotte, North Carolina, United States, 28204
Exelixis Clinical Site #19
Durham, North Carolina, United States, 27710
United States, Ohio
Exelixis Clinical Site #7
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Exelixis Clinical Site #5
Easton, Pennsylvania, United States, 18045
Exelixis Clinical Site #1
Philadelphia, Pennsylvania, United States, 19104
Exelixis Clinical Site #75
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Exelixis Clinical Site #134
Charleston, South Carolina, United States, 29425
United States, Tennessee
Exelixis Clinical Site #68
Nashville, Tennessee, United States, 37232
United States, Texas
Exelixis Clinical Site #8
Houston, Texas, United States, 77030
United States, Washington
Exelixis Clinical Site #113
Seattle, Washington, United States, 98109
Argentina
Exelixis Clinical Site #97
Caba, Argentina, C1012AAR
Exelixis Clinical Site #129
Córdoba, Argentina, X5000AVE
Argentina, Buenos Aires
Exelixis Clinical Site #96
Pergamino, Buenos Aires, Argentina, B2700CPM
Australia
Exelixis Clinical Site #12
Herston, Australia, 4029
Australia, New South Wales
Exelixis Clinical Site #17
St. Leonards, New South Wales, Australia, 2065
Exelixis Clinical Site #25
Waratah, New South Wales, Australia, 2298
Australia, South Australia
Exelixis Clinical Site #86
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Exelixis Clinical Site #24
Melbourne, Victoria, Australia, 3004
Austria
Exelixis Clinical Site #62
Salzburg, Austria, 5020
Exelixis Clinical Site #119
Vienna, Austria, 1090
Belgium
Exelixis Clinical Site #90
Brussels, Belgium, 1000
Exelixis Clinical Site #31
Brussels, Belgium, 1200
Exelixis Clinical Site #26
Edegem, Belgium, 2650
Exelixis Clinical Site #74
Edegem, Belgium, 2650
Exelixis Clinical Site #100
Gent, Belgium, 9000
Exelixis Clinical Site #27
Namur, Belgium, 5000
Brazil
Exelixis Clinical Site #92
Rio De Janeiro, Brazil, 20231-050
Exelixis Clinical Site #47
Sao Paulo, Brazil, 01246-000
Brazil, Parana
Exelixis Clinical Site #35
Cascavel, Parana, Brazil, 85806-300
Brazil, Rio Grande Do Sul
Exelixis Clinical Site #39
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
Exelixis Clinical Site #140
Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
Exelixis Clinical Site #38
Porto Alegre, Rio Grande Do Sul, Brazil, 90110-270
Brazil, Sao Paulo
Exelixis Clinical Site #40
Sao Jose do Rio Preto, Sao Paulo, Brazil, 15090-000
Brazil, São Paulo
Exelixis Clinical Site #116
Ribeirão Preto, São Paulo, Brazil, 14051-140
Canada, Alberta
Exelixis Clinical Site #20
Calgary, Alberta, Canada, T2N 4N2
Exelixis Clinical Site #18
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
Exelixis Clinical Site #107
London, Ontario, Canada, N6A 5W9
Exelixis Clinical Site #83
Toronto, Ontario, Canada, M5G 2M9
Croatia
Exelixis Clinical Site #145
Osijek, Croatia, 31000
Exelixis Clinical Site #137
Zagreb, Croatia, 10000
Exelixis Clinical Site #138
Zagreb, Croatia, 10000
Czechia
Exelixis Clinical Site #105
Brno, Czechia, 656 53
Exelixis Clinical Site #104
Olomouc, Czechia, 779 00
France
Exelixis Clinical Site #102
Besançon, France, 25030
Exelixis Clinical Site #91
Lyon Cedex 08, France, 69373
Exelixis Clinical Site #82
Nice, France, 06189
Exelixis Clinical Site #152
Paris, France, 75013
Exelixis Clinical Site #95
Strasbourg Cedex, France, 67065
France, Bourgogne-Franche-Comte
Exelixis Clinical Site #32
Dijon, Bourgogne-Franche-Comte, France, 21079
France, Ile De France
Exelixis Clinical Site #44
Villejuif, Ile De France, France, 94805
France, Nouvelle - Aquitaine
Exelixis Clinical Site #67
Bordeaux, Nouvelle - Aquitaine, France, 33075
France, Pays De La Loire
Exelixis Clinical Site #45
Angers, Pays De La Loire, France, 4933
France, Provence-Alpes-Cote d'Azur
Exelixis Clinical Site #72
Marseille, Provence-Alpes-Cote d'Azur, France, 13915
Germany
Exelixis Clinical Site #155
Aachen, Germany, 52074
Exelixis Clinical Site #131
Bonn, Germany, 53127
Exelixis Clinical Site #154
Essen, Germany, 45147
Exelixis Clinical Site #160
Freiburg, Germany, 79106
Exelixis Clinical Site #159
Hamburg, Germany, 20246
Exelixis Clinical Site #139
München, Germany, 81377
Germany, Baden-Württemberg
Exelixis Clinical Site #121
Tübingen, Baden-Württemberg, Germany, 72076
Germany, Bayern
Exelixis Clinical Site #156
Würzburg, Bayern, Germany, 97080
Germany, Hesse
Exelixis Clinical Site #125
Marburg, Hesse, Germany, 35043
Germany, Lower Saxony
Exelixis Clinical Site #163
Hannover, Lower Saxony, Germany, 30625
Germany, Sachsen-Anhalt
Exelixis Clinical Site #124
Magdeburg, Sachsen-Anhalt, Germany, 39120
Germany, Saxony
Exelixis Clinical Site #151
Dresden, Saxony, Germany, 01307
Hong Kong
Exelixis Clinical Site #28
Hong Kong, Hong Kong
Hungary
Exelixis Clinical Site #46
Budapest, Hungary, 1122
Exelixis Clinical Site #37
Pecs, Hungary, 7624
Israel
Exelixis Clinical Site #43
Haifa, Israel, 3109601
Exelixis Clinical Site #41
Jerusalem, Israel, 9112001
Exelixis Clinical Site #58
Petah tikva, Israel, 4941492
Italy
Exelixis Clinical Site #103
Milano, Italy, 20133
Exelixis Clinical Site #110
Milano, Italy, 20141
Exelixis Clinical Site #115
Milano, Italy, 20149
Exelixis Clinical Site #108
Napoli, Italy, 80131
Exelixis Clinical Site #56
Napoli, Italy, 80131
Exelixis Clinical Site #123
Padova, Italy, 35128
Exelixis Clinical Site #87
Roma, Italy, 00144
Exelixis Clinical Site #127
Roma, Italy, 00161
Exelixis Clinical Site #111
Siena, Italy, 53100
Italy, CT
Exelixis Clinical Site #135
Catania, CT, Italy, 95122
Italy, Catania
Exelixis Clinical Site #109
Viagrande, Catania, Italy, 95029
Italy, Forlì - Cesena
Exelixis Clinical Site #132
Meldola, Forlì - Cesena, Italy, 47017
Italy, GE
Exelixis Clinical Site #144
Genova, GE, Italy, 16132
Italy, Milano
Exelixis Clinical Site #143
Rozzano, Milano, Italy, 20089
Italy, PI
Exelixis Clinical Site #29
Pisa, PI, Italy, 56124
Italy, TO
Exelixis Clinical Site #120
Torino, TO, Italy, 10126
Korea, Republic of
Exelixis Clinical Site #70
Busan, Korea, Republic of, 49267
Exelixis Clinical Site #79
Gyeonggi-do, Korea, Republic of, 10408
Exelixis Clinical Site #36
Seoul, Korea, Republic of, 03080
Exelixis Clinical Site #34
Seoul, Korea, Republic of, 05505
Mexico
Exelixis Clinical Site #133
Ciudad de Mèxico, Mexico, 06100
Exelixis Clinical Site #147
Ciudad de México, Mexico, 03100
Exelixis Clinical Site #148
Ciudad de México, Mexico, 06700
Exelixis Clinical Site #161
San Luis Potosí, Mexico, 78200
Mexico, Chiapas
Exelixis Clinical Site #158
Tuxtla Gutiérrez, Chiapas, Mexico, 29038
Netherlands, Noord-Holland
Exelixis Clinical Site #128
Amsterdam, Noord-Holland, Netherlands, 1081 HV
Netherlands, Zuid-Holland
Exelixis Clinical Site #117
Leiden, Zuid-Holland, Netherlands, 2333 ZA
Poland, Mazowieckie
Exelixis Clinical Site #15
Warszawa, Mazowieckie, Poland, 02-781
Poland, Slaskie
Exelixis Clinical Site #61
Gliwice, Slaskie, Poland, 44-101
Poland, Wielkopolskie
Exelixis Clinical Site #59
Poznan, Wielkopolskie, Poland, 60-355
Romania
Exelixis Clinical Site #146
Bucuresti, Romania, 011863
Romania, Cluj
Exelixis Clinical Site #149
Cluj-Napoca, Cluj, Romania, 400015
Romania, Dolj
Exelixis Clinical Site #150
Craiova, Dolj, Romania, 200385
Romania, Timis
Exelixis Clinical Site #142
Timişoara, Timis, Romania, 300166
Russian Federation
Exelixis Clinical Site #49
Moscow, Russian Federation, 117036
Exelixis Clinical Site #53
Moscow, Russian Federation, 121309
Exelixis Clinical Site #84
Moscow, Russian Federation, 125284
Exelixis Clinical Site #85
Moscow, Russian Federation, 155478
Exelixis Clinical Site #106
Omsk, Russian Federation, 644013
Exelixis Clinical Site #89
Saint Petersburg, Russian Federation, 198255
Exelixis Clinical Site #52
Samara, Russian Federation, 443031
Exelixis Clinical Site #66
Yaroslavl, Russian Federation, 150054
Russian Federation, Kaluzhiskiy Region
Exelixis Clinical Site #48
Obninsk, Kaluzhiskiy Region, Russian Federation, 249036
Russian Federation, Kursk Region
Exelixis Clinical Site #55
Kislino, Kursk Region, Russian Federation, 305524
Russian Federation, Tyumen Region
Exelixis Clinical Site #157
Tyumen, Tyumen Region, Russian Federation, 625041
Spain
Exelixis Clinical Site #14
Barcelona, Spain, 08035
Exelixis Clinical Site #99
Barcelona, Spain, 08036
Exelixis Clinical Site #114
Madrid, Spain, 28027
Exelixis Clinical Site #30
Madrid, Spain, 28033
Exelixis Clinical Site #13
Madrid, Spain, 28034
Exelixis Clinical Site #16
Madrid, Spain, 28040
Exelixis Clinical Site #33
Madrid, Spain, 28041
Exelixis Clinical Site #73
Madrid, Spain, 28046
Exelixis Clinical Site #23
Madrid, Spain, 28050
Exelixis Clinical Site #81
Málaga, Spain, 29010
Taiwan
Exelixis Clinical Site #136
Tainan, Taiwan, 704
Exelixis Clinical Site #112
Tainan, Taiwan, 71004
Exelixis Clinical Site #77
Taipei, Taiwan, 10002
Exelixis Clinical Site #101
Taipei, Taiwan, 11490
Thailand, Bangkok
Exelixis Clinical Site #126
Bangkok Noi, Bangkok, Thailand, 10700
Exelixis Clinical Site #122
Pathum Wan, Bangkok, Thailand, 10330
Exelixis Clinical Site #141
Ratchathewi, Bangkok, Thailand, 10400
Thailand, Songkla
Exelixis Clinical Site #130
Hat Yai, Songkla, Thailand, 90110
United Kingdom
Exelixis Clinical Site #65
Manchester, United Kingdom, M20 4BX
Exelixis Clinical Site #57
Sheffield, United Kingdom, S10 2SJ
United Kingdom, England
Exelixis Clinical Site #88
Birmingham, England, United Kingdom, B15 2TH
Exelixis Clinical Site #71
Bristol, England, United Kingdom, BS2 8ED
Exelixis Clinical Site #162
London, England, United Kingdom, SW3 6JJ
Exelixis Clinical Site #51
Oxford, England, United Kingdom, OX3 7LE
United Kingdom, Scotland
Exelixis Clinical Site #64
Aberdeen, Scotland, United Kingdom, AB25 2ZN
Exelixis Clinical Site #50
Glasgow, Scotland, United Kingdom, G12 0YN
United Kingdom, Wales
Exelixis Clinical Site #60
Cardiff, Wales, United Kingdom, CF14 2TL
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol and Statistical Analysis Plan
Document Date: April 30, 2018
Uploaded: 11/10/2021 15:48
File Name: Prot_SAP_000.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details
 
Arm/Group Title Cabozantinib Placebo
Arm/Group Description

cabozantinib (60 mg) once daily orally (qd)

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

placebo once daily orally (qd)

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

Period Title: Overall Study
Started 125 62
Completed 89 26
Not Completed 36 36
Reason Not Completed
Adverse Event 8 1
Radiographic Progression 14 29
Clinical deterioration 10 6
Withdrawal by Subject 2 0
Lack of Efficacy 1 0
Lost to Follow-up 1 0
Open or close this module Baseline Characteristics
Arm/Group TitleCabozantinibPlaceboTotal
Arm/Group Description

cabozantinib (60 mg) once daily orally (qd)

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

placebo once daily orally (qd)

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

Total of all reporting groups
Overall Number of Baseline Participants 125 62 187
Baseline Analysis Population Description [Not Specified]
Age, Categorical
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed125 Participants62 Participants187 Participants
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
62
49.6%
29
46.77%
91
48.66%
>=65 years
63
50.4%
33
53.23%
96
51.34%
Age, Continuous
Median (Full Range)
Unit of measure: years
Number Analyzed125 Participants62 Participants187 Participants
65(32 to 85)66(37 to 81)66(32 to 85)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed125 Participants62 Participants187 Participants
Female
68
54.4%
34
54.84%
102
54.55%
Male
57
45.6%
28
45.16%
85
45.45%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed125 Participants62 Participants187 Participants
Hispanic or Latino
21
16.8%
6
9.68%
27
14.44%
Not Hispanic or Latino
95
76%
53
85.48%
148
79.14%
Unknown or Not Reported
9
7.2%
3
4.84%
12
6.42%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed125 Participants62 Participants187 Participants
American Indian or Alaska Native
3
2.4%
0
0%
3
1.6%
Asian
20
16%
14
22.58%
34
18.18%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
0.8%
2
3.23%
3
1.6%
White
90
72%
41
66.13%
131
70.05%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
11
8.8%
5
8.06%
16
8.56%
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed125 Participants62 Participants187 Participants
Hong Kong
011
United States
10919
Czechia
101
Thailand
213
Russia
8311
Austria
404
Netherlands
112
South Korea
8816
Brazil
11415
Poland
9413
France
8311
Croatia
101
Argentina
101
Romania
314
Hungary
538
United Kingdom
437
Spain
10919
Canada
303
Belgium
325
Taiwan
639
Italy
14519
Mexico
303
Israel
303
Australia
516
Germany
213
Receipt of prior lenvatinib
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed125 Participants62 Participants187 Participants
7939118
Open or close this module Outcome Measures
1. Primary Outcome:
Title Progression Free Survival (PFS)
Description Time to the earlier of either radiographic progressive disease (PD) or death from any cause.
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.
Outcome Measure Data
Analysis Population Description
All subjects randomized at the time of the analysis (N=187).
 
Arm/Group TitleCabozantinibPlacebo
Arm/Group Description

cabozantinib (60 mg) once daily orally (qd)

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

placebo once daily orally (qd)

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

Overall Number of Participants Analyzed125 62
Median (96% Confidence Interval)
Unit of Measure: months
NA(5.7 to NA) [1] 1.9(1.8 to 3.6)
[1]NA Explanation: NA explanation: non-evaluable

Quality Control Review Comment provided by the National Library of Medicine:

  1. The explanation provided is not sufficient to understand why one or more values are not available.
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionCabozantinib, Placebo
Comments[Not specified]
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value< 0.0001
Comments[Not specified]
MethodLog Rank
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value0.22
Confidence Interval(2-sided) 96%
0.13 to 0.36
Estimation Comments[Not specified]
2. Primary Outcome:
Title Objective Response Rate (ORR)
Description Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).
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.
Outcome Measure Data
Analysis Population Description
The first 100 subjects randomized.
 
Arm/Group TitleCabozantinibPlacebo
Arm/Group Description

cabozantinib (60 mg) once daily orally (qd)

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

placebo once daily orally (qd)

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

Overall Number of Participants Analyzed125 62
Number (99% Confidence Interval)
Unit of Measure: percentage of participants
15(5.8 to 29.3) 0(0.0 to 14.8)

Quality Control Review Comment provided by the National Library of Medicine:

  1. The number of participants analyzed appears inconsistent with data here or in other parts of the record.
Open or close this module Adverse Events
 
Time Frame 1 year, 8 months.
Adverse Event Reporting Description Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
 
Arm/Group Title Cabozantinib Placebo
Arm/Group Description

cabozantinib (60 mg) once daily orally (qd)

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

placebo once daily orally (qd)

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

All-Cause Mortality
  CabozantinibPlacebo
 Affected / At Risk (%)Affected / At Risk (%)
Total 17 / 125 (13.6%)10 / 62 (16.13%)
Serious Adverse Events
  CabozantinibPlacebo
 Affected / At Risk (%)Affected / At Risk (%)
Total 43 / 125 (34.4%)18 / 62 (29.03%)
Blood and lymphatic system disorders
Anaemia † A 1 / 125 (0.8%)0 / 62 (0%)
Cardiac disorders
Atrial fibrillation † A 2 / 125 (1.6%)0 / 62 (0%)
Cardiac arrest † A 1 / 125 (0.8%)1 / 62 (1.61%)
Cardio-respiratory arrest † A 1 / 125 (0.8%)0 / 62 (0%)
Gastrointestinal disorders
Abdominal distension † A 1 / 125 (0.8%)0 / 62 (0%)
Ascites † A 1 / 125 (0.8%)0 / 62 (0%)
Diarrhoea † A 4 / 125 (3.2%)0 / 62 (0%)
Intestinal obstruction † A 1 / 125 (0.8%)0 / 62 (0%)
Large intestine perforation † A 1 / 125 (0.8%)0 / 62 (0%)
Oesophageal stenosis † A 1 / 125 (0.8%)0 / 62 (0%)
Vomiting † A 1 / 125 (0.8%)0 / 62 (0%)
General disorders
Chest pain † A 1 / 125 (0.8%)0 / 62 (0%)
Disease progression † A 3 / 125 (2.4%)0 / 62 (0%)
Fatigue † A 1 / 125 (0.8%)0 / 62 (0%)
General physical health deterioration † A 3 / 125 (2.4%)0 / 62 (0%)
Oedema peripheral † A 1 / 125 (0.8%)1 / 62 (1.61%)
Pain † A 1 / 125 (0.8%)1 / 62 (1.61%)
Hepatobiliary disorders
Cholangitis † A 1 / 125 (0.8%)0 / 62 (0%)
Cholangitis acute † A 1 / 125 (0.8%)0 / 62 (0%)
Cholelithiasis † A 1 / 125 (0.8%)0 / 62 (0%)
Jaundice cholestatic † A 1 / 125 (0.8%)0 / 62 (0%)
Infections and infestations
Anal abscess † A 1 / 125 (0.8%)0 / 62 (0%)
Bronchitis † A 1 / 125 (0.8%)0 / 62 (0%)
COVID-19 † A 1 / 125 (0.8%)1 / 62 (1.61%)
Influenza † A 0 / 125 (0%)1 / 62 (1.61%)
Lower respiratory tract infection † A 0 / 125 (0%)1 / 62 (1.61%)
Pneumonia † A 2 / 125 (1.6%)1 / 62 (1.61%)
Rectal abscess † A 1 / 125 (0.8%)0 / 62 (0%)
Suspected COVID-19 † A 1 / 125 (0.8%)0 / 62 (0%)
Injury, poisoning and procedural complications
Spinal fracture † A 0 / 125 (0%)1 / 62 (1.61%)
Metabolism and nutrition disorders
Decreased appetite † A 1 / 125 (0.8%)0 / 62 (0%)
Dehydration † A 1 / 125 (0.8%)0 / 62 (0%)
Electrolyte imbalance † A 1 / 125 (0.8%)0 / 62 (0%)
Hypercalcaemia † A 1 / 125 (0.8%)1 / 62 (1.61%)
Hypocalcaemia † A 2 / 125 (1.6%)0 / 62 (0%)
Hyponatraemia † A 0 / 125 (0%)1 / 62 (1.61%)
Musculoskeletal and connective tissue disorders
Arthralgia † A 1 / 125 (0.8%)0 / 62 (0%)
Back pain † A 1 / 125 (0.8%)0 / 62 (0%)
Bone lesion † A 2 / 125 (1.6%)0 / 62 (0%)
Muscle haemorrhage † A 1 / 125 (0.8%)0 / 62 (0%)
Musculoskeletal pain † A 2 / 125 (1.6%)0 / 62 (0%)
Osteonecrosis of jaw † A 1 / 125 (0.8%)0 / 62 (0%)
Pain in jaw † A 0 / 125 (0%)1 / 62 (1.61%)
Pathological fracture † A 2 / 125 (1.6%)0 / 62 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer † A 3 / 125 (2.4%)0 / 62 (0%)
Thyroid cancer metastatic † A 1 / 125 (0.8%)0 / 62 (0%)
Tumour pain † A 0 / 125 (0%)1 / 62 (1.61%)
Nervous system disorders
Carotid artery stenosis † A 0 / 125 (0%)1 / 62 (1.61%)
Dementia Alzheimer's type † A 1 / 125 (0.8%)0 / 62 (0%)
Spinal cord compression † A 1 / 125 (0.8%)0 / 62 (0%)
Psychiatric disorders
Confusional state † A 1 / 125 (0.8%)0 / 62 (0%)
Renal and urinary disorders
Acute kidney injury † A 1 / 125 (0.8%)0 / 62 (0%)
Renal failure † A 1 / 125 (0.8%)0 / 62 (0%)
Renal impairment † A 1 / 125 (0.8%)0 / 62 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea † A 4 / 125 (3.2%)4 / 62 (6.45%)
Haemoptysis † A 2 / 125 (1.6%)0 / 62 (0%)
Hydrothorax † A 0 / 125 (0%)1 / 62 (1.61%)
Laryngeal necrosis † A 1 / 125 (0.8%)0 / 62 (0%)
Lung disorder † A 1 / 125 (0.8%)0 / 62 (0%)
Pleural effusion † A 4 / 125 (3.2%)3 / 62 (4.84%)
Pneumonitis † A 1 / 125 (0.8%)0 / 62 (0%)
Pneumothorax † A 1 / 125 (0.8%)0 / 62 (0%)
Pulmonary embolism † A 4 / 125 (3.2%)0 / 62 (0%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome † A 1 / 125 (0.8%)0 / 62 (0%)
Pruritus † A 0 / 125 (0%)1 / 62 (1.61%)
Vascular disorders
Arterial haemorrhage † A 1 / 125 (0.8%)0 / 62 (0%)
Deep vein thrombosis † A 2 / 125 (1.6%)0 / 62 (0%)
Hypertension † A 2 / 125 (1.6%)0 / 62 (0%)
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 23.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  CabozantinibPlacebo
 Affected / At Risk (%)Affected / At Risk (%)
Total 112 / 125 (89.6%)32 / 62 (51.61%)
Blood and lymphatic system disorders
Anaemia † A 8 / 125 (6.4%)0 / 62 (0%)
Anaemia † A 8 / 125 (6.4%)8 / 62 (12.9%)
Thrombocytopenia † A 9 / 125 (7.2%)0 / 62 (0%)
Gastrointestinal disorders
Abdominal pain † A 12 / 125 (9.6%)2 / 62 (3.23%)
Constipation † A 14 / 125 (11.2%)5 / 62 (8.06%)
Diarrhoea † A 69 / 125 (55.2%)2 / 62 (3.23%)
Dry mouth † A 13 / 125 (10.4%)1 / 62 (1.61%)
Dyspepsia † A 7 / 125 (5.6%)1 / 62 (1.61%)
Nausea † A 33 / 125 (26.4%)1 / 62 (1.61%)
Stomatitis † A 20 / 125 (16%)2 / 62 (3.23%)
Vomiting † A 18 / 125 (14.4%)5 / 62 (8.06%)
General disorders
Asthenia † A 21 / 125 (16.8%)9 / 62 (14.52%)
Fatigue † A 41 / 125 (32.8%)5 / 62 (8.06%)
Mucosal inflammation † A 18 / 125 (14.4%)0 / 62 (0%)
Infections and infestations
Urinary tract infection † A 8 / 125 (6.4%)2 / 62 (3.23%)
Investigations
Alanine aminotransferase increased † A 32 / 125 (25.6%)1 / 62 (1.61%)
Aspartate aminotransferase increased † A 32 / 125 (25.6%)1 / 62 (1.61%)
Blood alkaline phosphatase increased † A 13 / 125 (10.4%)2 / 62 (3.23%)
Blood lactate dehydrogenase increased † A 12 / 125 (9.6%)0 / 62 (0%)
Neutrophil count decreased † A 7 / 125 (5.6%)1 / 62 (1.61%)
Platelet count decreased † A 8 / 125 (6.4%)1 / 62 (1.61%)
Weight decreased † A 25 / 125 (20%)3 / 62 (4.84%)
Metabolism and nutrition disorders
Decreased appetite † A 33 / 125 (26.4%)10 / 62 (16.13%)
Hypocalcaemia † A 30 / 125 (24%)1 / 62 (1.61%)
Hypokalaemia † A 11 / 125 (8.8%)1 / 62 (1.61%)
Hypomagnesaemia † A 18 / 125 (14.4%)3 / 62 (4.84%)
Musculoskeletal and connective tissue disorders
Arthralgia † A 11 / 125 (8.8%)4 / 62 (6.45%)
Back pain † A 8 / 125 (6.4%)3 / 62 (4.84%)
Muscle spasms † A 8 / 125 (6.4%)1 / 62 (1.61%)
Pain in extremity † A 8 / 125 (6.4%)3 / 62 (4.84%)
Nervous system disorders
Dysgeusia † A 14 / 125 (11.2%)0 / 62 (0%)
Headache † A 14 / 125 (11.2%)1 / 62 (1.61%)
Renal and urinary disorders
Proteinuria † A 21 / 125 (16.8%)2 / 62 (3.23%)
Respiratory, thoracic and mediastinal disorders
Dysphonia † A 15 / 125 (12%)1 / 62 (1.61%)
Dyspnoea † A 20 / 125 (16%)9 / 62 (14.52%)
Skin and subcutaneous tissue disorders
Alopecia † A 8 / 125 (6.4%)1 / 62 (1.61%)
Palmar-plantar erythrodysaesthesia syndrome † A 59 / 125 (47.2%)0 / 62 (0%)
Vascular disorders
Hypertension † A 37 / 125 (29.6%)3 / 62 (4.84%)
Indicates events were collected by systematic assessment.
ATerm from vocabulary, MedDRA 23.0
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Our agreements with investigators vary; constant is our right to review results communications prior to public release, and embargo communications for a period of ≤ 60 days from submittal for review. We do not prohibit investigators from publishing, but we may require previously undisclosed confidential information, other than study results, to be removed from publications, and single-center publications are postponed until after publication of the trial's primary multicenter publication.
Results Point of Contact:
Name/Official Title:
Exelixis Medical Information
Organization:
Exelixis, Inc.
Phone:
855-292-3935
Email:
druginfo@exelixis.com

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