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

Differentiated Thyroid Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03690388
• Other study ID #: XL184-311
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 5, 2018
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 (VEGFR)-Targeted therapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 187
• Est. completion date: December 2024
• Est. primary completion date: August 19, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Differentiated Thyroid Cancer
• Thyroid Diseases
• Thyroid Neoplasms

Intervention

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Exelixis	Ipsen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Croatia,  Czechia,  France,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Romania,  Russian Federation,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.