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
Sponsor
Exelixis (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03690388
Collaborator
(none)
258
164
2
49.9
1.6
0
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
258 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
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.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 (Participant, Care Provider, Investigator)
Masking Description:
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).
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Oct 5, 2018
Actual Primary Completion Date
:
Aug 19, 2020
Anticipated Study Completion Date
:
Dec 1, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cabozantinib cabozantinib (60 mg) once daily orally (qd) |
Drug: Cabozantinib
Tablets containing 60-mg or 20-mg cabozantinib once daily orally.
Other Names:
|
| Placebo Comparator: Placebo placebo once daily orally (qd) |
Drug: Placebo
Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival (PFS) [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.
- Objective Response Rate (ORR) [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).
Eligibility Criteria
Criteria
Ages Eligible for Study:
16 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Exelixis Clinical Site #2 | Newport Beach | California | United States | 92658 |
| 2 | Exelixis Clinical Site #98 | Sacramento | California | United States | 95817 |
| 3 | Exelixis Clinical Site #69 | San Francisco | California | United States | 94115 |
| 4 | Exelixis Clinical Site #10 | Stanford | California | United States | 94305 |
| 5 | Exelixis Clinical Site #3 | Torrance | California | United States | 90502 |
| 6 | Exelixis Clinical Site #9 | Aurora | Colorado | United States | 80045 |
| 7 | Exelixis Clinical Site #21 | New Haven | Connecticut | United States | 06510 |
| 8 | Exelixis Clinical Site #4 | Washington | District of Columbia | United States | 20010 |
| 9 | Exelixis Clinical Site #94 | Miami | Florida | United States | 33136 |
| 10 | Exelixis Clinical Site #93 | Orlando | Florida | United States | 32804 |
| 11 | Exelixis Clinical Site #6 | Tampa | Florida | United States | 33612 |
| 12 | Exelixis Clinical Site #164 | Chicago | Illinois | United States | 60637 |
| 13 | Exelixis Clinical Site #54 | Lexington | Kentucky | United States | 40536 |
| 14 | Exelixis Clinical Site #153 | Boston | Massachusetts | United States | 02114 |
| 15 | Exelixis Clinical Site #80 | Ann Arbor | Michigan | United States | 48109 |
| 16 | Exelixis Clinical Site #78 | Detroit | Michigan | United States | 48201 |
| 17 | Exelixis Clinical Site #22 | Detroit | Michigan | United States | 48202 |
| 18 | Exelixis Clinical Site #63 | Columbia | Missouri | United States | 65212 |
| 19 | Exelixis Clinical Site #42 | Saint Louis | Missouri | United States | 63110 |
| 20 | Exelixis Clinical Site #11 | Omaha | Nebraska | United States | 68114 |
| 21 | Exelixis Clinical Site #118 | Morristown | New Jersey | United States | 07962 |
| 22 | Exelixis Clinical Site #76 | Charlotte | North Carolina | United States | 28204 |
| 23 | Exelixis Clinical Site #19 | Durham | North Carolina | United States | 27710 |
| 24 | Exelixis Clinical Site #7 | Cincinnati | Ohio | United States | 45219 |
| 25 | Exelixis Clinical Site #5 | Easton | Pennsylvania | United States | 18045 |
| 26 | Exelixis Clinical Site #1 | Philadelphia | Pennsylvania | United States | 19104 |
| 27 | Exelixis Clinical Site #75 | Pittsburgh | Pennsylvania | United States | 15232 |
| 28 | Exelixis Clinical Site #134 | Charleston | South Carolina | United States | 29425 |
| 29 | Exelixis Clinical Site #68 | Nashville | Tennessee | United States | 37232 |
| 30 | Exelixis Clinical Site #8 | Houston | Texas | United States | 77030 |
| 31 | Exelixis Clinical Site #113 | Seattle | Washington | United States | 98109 |
| 32 | Exelixis Clinical Site #96 | Pergamino | Buenos Aires | Argentina | B2700CPM |
| 33 | Exelixis Clinical Site #97 | Caba | Argentina | C1012AAR | |
| 34 | Exelixis Clinical Site #129 | Córdoba | Argentina | X5000AVE | |
| 35 | Exelixis Clinical Site #17 | St. Leonards | New South Wales | Australia | 2065 |
| 36 | Exelixis Clinical Site #25 | Waratah | New South Wales | Australia | 2298 |
| 37 | Exelixis Clinical Site #86 | Bedford Park | South Australia | Australia | 5042 |
| 38 | Exelixis Clinical Site #24 | Melbourne | Victoria | Australia | 3004 |
| 39 | Exelixis Clinical Site #12 | Herston | Australia | 4029 | |
| 40 | Exelixis Clinical Site #62 | Salzburg | Austria | 5020 | |
| 41 | Exelixis Clinical Site #119 | Vienna | Austria | 1090 | |
| 42 | Exelixis Clinical Site #90 | Brussels | Belgium | 1000 | |
| 43 | Exelixis Clinical Site #31 | Brussels | Belgium | 1200 | |
| 44 | Exelixis Clinical Site #26 | Edegem | Belgium | 2650 | |
| 45 | Exelixis Clinical Site #74 | Edegem | Belgium | 2650 | |
| 46 | Exelixis Clinical Site #100 | Gent | Belgium | 9000 | |
| 47 | Exelixis Clinical Site #27 | Namur | Belgium | 5000 | |
| 48 | Exelixis Clinical Site #35 | Cascavel | Parana | Brazil | 85806-300 |
| 49 | Exelixis Clinical Site #39 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 50 | Exelixis Clinical Site #140 | Porto Alegre | Rio Grande Do Sul | Brazil | 90050-170 |
| 51 | Exelixis Clinical Site #38 | Porto Alegre | Rio Grande Do Sul | Brazil | 90110-270 |
| 52 | Exelixis Clinical Site #40 | Sao Jose do Rio Preto | Sao Paulo | Brazil | 15090-000 |
| 53 | Exelixis Clinical Site #116 | Ribeirão Preto | São Paulo | Brazil | 14051-140 |
| 54 | Exelixis Clinical Site #92 | Rio De Janeiro | Brazil | 20231-050 | |
| 55 | Exelixis Clinical Site #47 | Sao Paulo | Brazil | 01246-000 | |
| 56 | Exelixis Clinical Site #20 | Calgary | Alberta | Canada | T2N 4N2 |
| 57 | Exelixis Clinical Site #18 | Edmonton | Alberta | Canada | T6G 1Z2 |
| 58 | Exelixis Clinical Site #107 | London | Ontario | Canada | N6A 5W9 |
| 59 | Exelixis Clinical Site #83 | Toronto | Ontario | Canada | M5G 2M9 |
| 60 | Exelixis Clinical Site #145 | Osijek | Croatia | 31000 | |
| 61 | Exelixis Clinical Site #137 | Zagreb | Croatia | 10000 | |
| 62 | Exelixis Clinical Site #138 | Zagreb | Croatia | 10000 | |
| 63 | Exelixis Clinical Site #105 | Brno | Czechia | 656 53 | |
| 64 | Exelixis Clinical Site #104 | Olomouc | Czechia | 779 00 | |
| 65 | Exelixis Clinical Site #32 | Dijon | Bourgogne-Franche-Comte | France | 21079 |
| 66 | Exelixis Clinical Site #44 | Villejuif | Ile De France | France | 94805 |
| 67 | Exelixis Clinical Site #67 | Bordeaux | Nouvelle - Aquitaine | France | 33075 |
| 68 | Exelixis Clinical Site #45 | Angers | Pays De La Loire | France | 4933 |
| 69 | Exelixis Clinical Site #72 | Marseille | Provence-Alpes-Cote d'Azur | France | 13915 |
| 70 | Exelixis Clinical Site #102 | Besançon | France | 25030 | |
| 71 | Exelixis Clinical Site #91 | Lyon Cedex 08 | France | 69373 | |
| 72 | Exelixis Clinical Site #82 | Nice | France | 06189 | |
| 73 | Exelixis Clinical Site #152 | Paris | France | 75013 | |
| 74 | Exelixis Clinical Site #95 | Strasbourg Cedex | France | 67065 | |
| 75 | Exelixis Clinical Site #121 | Tübingen | Baden-Württemberg | Germany | 72076 |
| 76 | Exelixis Clinical Site #156 | Würzburg | Bayern | Germany | 97080 |
| 77 | Exelixis Clinical Site #125 | Marburg | Hesse | Germany | 35043 |
| 78 | Exelixis Clinical Site #163 | Hannover | Lower Saxony | Germany | 30625 |
| 79 | Exelixis Clinical Site #124 | Magdeburg | Sachsen-Anhalt | Germany | 39120 |
| 80 | Exelixis Clinical Site #151 | Dresden | Saxony | Germany | 01307 |
| 81 | Exelixis Clinical Site #155 | Aachen | Germany | 52074 | |
| 82 | Exelixis Clinical Site #131 | Bonn | Germany | 53127 | |
| 83 | Exelixis Clinical Site #154 | Essen | Germany | 45147 | |
| 84 | Exelixis Clinical Site #160 | Freiburg | Germany | 79106 | |
| 85 | Exelixis Clinical Site #159 | Hamburg | Germany | 20246 | |
| 86 | Exelixis Clinical Site #139 | München | Germany | 81377 | |
| 87 | Exelixis Clinical Site #28 | Hong Kong | Hong Kong | ||
| 88 | Exelixis Clinical Site #46 | Budapest | Hungary | 1122 | |
| 89 | Exelixis Clinical Site #37 | Pecs | Hungary | 7624 | |
| 90 | Exelixis Clinical Site #43 | Haifa | Israel | 3109601 | |
| 91 | Exelixis Clinical Site #41 | Jerusalem | Israel | 9112001 | |
| 92 | Exelixis Clinical Site #58 | Petah tikva | Israel | 4941492 | |
| 93 | Exelixis Clinical Site #109 | Viagrande | Catania | Italy | 95029 |
| 94 | Exelixis Clinical Site #135 | Catania | CT | Italy | 95122 |
| 95 | Exelixis Clinical Site #132 | Meldola | Forlì - Cesena | Italy | 47017 |
| 96 | Exelixis Clinical Site #144 | Genova | GE | Italy | 16132 |
| 97 | Exelixis Clinical Site #143 | Rozzano | Milano | Italy | 20089 |
| 98 | Exelixis Clinical Site #29 | Pisa | PI | Italy | 56124 |
| 99 | Exelixis Clinical Site #120 | Torino | TO | Italy | 10126 |
| 100 | Exelixis Clinical Site #103 | Milano | Italy | 20133 | |
| 101 | Exelixis Clinical Site #110 | Milano | Italy | 20141 | |
| 102 | Exelixis Clinical Site #115 | Milano | Italy | 20149 | |
| 103 | Exelixis Clinical Site #108 | Napoli | Italy | 80131 | |
| 104 | Exelixis Clinical Site #56 | Napoli | Italy | 80131 | |
| 105 | Exelixis Clinical Site #123 | Padova | Italy | 35128 | |
| 106 | Exelixis Clinical Site #87 | Roma | Italy | 00144 | |
| 107 | Exelixis Clinical Site #127 | Roma | Italy | 00161 | |
| 108 | Exelixis Clinical Site #111 | Siena | Italy | 53100 | |
| 109 | Exelixis Clinical Site #70 | Busan | Korea, Republic of | 49267 | |
| 110 | Exelixis Clinical Site #79 | Gyeonggi-do | Korea, Republic of | 10408 | |
| 111 | Exelixis Clinical Site #36 | Seoul | Korea, Republic of | 03080 | |
| 112 | Exelixis Clinical Site #34 | Seoul | Korea, Republic of | 05505 | |
| 113 | Exelixis Clinical Site #158 | Tuxtla Gutiérrez | Chiapas | Mexico | 29038 |
| 114 | Exelixis Clinical Site #133 | Ciudad de Mèxico | Mexico | 06100 | |
| 115 | Exelixis Clinical Site #147 | Ciudad de México | Mexico | 03100 | |
| 116 | Exelixis Clinical Site #148 | Ciudad de México | Mexico | 06700 | |
| 117 | Exelixis Clinical Site #161 | San Luis Potosí | Mexico | 78200 | |
| 118 | Exelixis Clinical Site #128 | Amsterdam | Noord-Holland | Netherlands | 1081 HV |
| 119 | Exelixis Clinical Site #117 | Leiden | Zuid-Holland | Netherlands | 2333 ZA |
| 120 | Exelixis Clinical Site #15 | Warszawa | Mazowieckie | Poland | 02-781 |
| 121 | Exelixis Clinical Site #61 | Gliwice | Slaskie | Poland | 44-101 |
| 122 | Exelixis Clinical Site #59 | Poznan | Wielkopolskie | Poland | 60-355 |
| 123 | Exelixis Clinical Site #149 | Cluj-Napoca | Cluj | Romania | 400015 |
| 124 | Exelixis Clinical Site #150 | Craiova | Dolj | Romania | 200385 |
| 125 | Exelixis Clinical Site #142 | Timişoara | Timis | Romania | 300166 |
| 126 | Exelixis Clinical Site #146 | Bucuresti | Romania | 011863 | |
| 127 | Exelixis Clinical Site #48 | Obninsk | Kaluzhiskiy Region | Russian Federation | 249036 |
| 128 | Exelixis Clinical Site #55 | Kislino | Kursk Region | Russian Federation | 305524 |
| 129 | Exelixis Clinical Site #157 | Tyumen | Tyumen Region | Russian Federation | 625041 |
| 130 | Exelixis Clinical Site #49 | Moscow | Russian Federation | 117036 | |
| 131 | Exelixis Clinical Site #53 | Moscow | Russian Federation | 121309 | |
| 132 | Exelixis Clinical Site #84 | Moscow | Russian Federation | 125284 | |
| 133 | Exelixis Clinical Site #85 | Moscow | Russian Federation | 155478 | |
| 134 | Exelixis Clinical Site #106 | Omsk | Russian Federation | 644013 | |
| 135 | Exelixis Clinical Site #89 | Saint Petersburg | Russian Federation | 198255 | |
| 136 | Exelixis Clinical Site #52 | Samara | Russian Federation | 443031 | |
| 137 | Exelixis Clinical Site #66 | Yaroslavl | Russian Federation | 150054 | |
| 138 | Exelixis Clinical Site #14 | Barcelona | Spain | 08035 | |
| 139 | Exelixis Clinical Site #99 | Barcelona | Spain | 08036 | |
| 140 | Exelixis Clinical Site #114 | Madrid | Spain | 28027 | |
| 141 | Exelixis Clinical Site #30 | Madrid | Spain | 28033 | |
| 142 | Exelixis Clinical Site #13 | Madrid | Spain | 28034 | |
| 143 | Exelixis Clinical Site #16 | Madrid | Spain | 28040 | |
| 144 | Exelixis Clinical Site #33 | Madrid | Spain | 28041 | |
| 145 | Exelixis Clinical Site #73 | Madrid | Spain | 28046 | |
| 146 | Exelixis Clinical Site #23 | Madrid | Spain | 28050 | |
| 147 | Exelixis Clinical Site #81 | Málaga | Spain | 29010 | |
| 148 | Exelixis Clinical Site #136 | Tainan | Taiwan | 704 | |
| 149 | Exelixis Clinical Site #112 | Tainan | Taiwan | 71004 | |
| 150 | Exelixis Clinical Site #77 | Taipei | Taiwan | 10002 | |
| 151 | Exelixis Clinical Site #101 | Taipei | Taiwan | 11490 | |
| 152 | Exelixis Clinical Site #126 | Bangkok Noi | Bangkok | Thailand | 10700 |
| 153 | Exelixis Clinical Site #122 | Pathum Wan | Bangkok | Thailand | 10330 |
| 154 | Exelixis Clinical Site #141 | Ratchathewi | Bangkok | Thailand | 10400 |
| 155 | Exelixis Clinical Site #130 | Hat Yai | Songkla | Thailand | 90110 |
| 156 | Exelixis Clinical Site #88 | Birmingham | England | United Kingdom | B15 2TH |
| 157 | Exelixis Clinical Site #71 | Bristol | England | United Kingdom | BS2 8ED |
| 158 | Exelixis Clinical Site #162 | London | England | United Kingdom | SW3 6JJ |
| 159 | Exelixis Clinical Site #51 | Oxford | England | United Kingdom | OX3 7LE |
| 160 | Exelixis Clinical Site #64 | Aberdeen | Scotland | United Kingdom | AB25 2ZN |
| 161 | Exelixis Clinical Site #50 | Glasgow | Scotland | United Kingdom | G12 0YN |
| 162 | Exelixis Clinical Site #60 | Cardiff | Wales | United Kingdom | CF14 2TL |
| 163 | Exelixis Clinical Site #65 | Manchester | United Kingdom | M20 4BX | |
| 164 | Exelixis Clinical Site #57 | Sheffield | United Kingdom | S10 2SJ |
Sponsors and Collaborators
- Exelixis
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Exelixis
ClinicalTrials.gov Identifier:
NCT03690388
Other Study ID Numbers:
- XL184-311
First Posted:
Oct 1, 2018
Last Update Posted:
Jul 15, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Exelixis
Additional relevant MeSH terms: