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Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib (CELESTIAL)

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Cabozantinib tablets
Placebo tablets
Sponsored by
Exelixis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring cabozantinib, XL184, liver cancer, hepatocellular carcinoma, tyrosine kinase inhibitor, MET kinase, vascular endothelial growth factor receptor 2 (VEGFR2)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Select Inclusion Criteria:

  1. Histological or cytological diagnosis of HCC.
  2. The subject has disease that is not amenable to a curative treatment approach.
  3. Received prior sorafenib.
  4. Progression following at least 1 prior systemic treatment for HCC.
  5. Recovery to from toxicities related to any prior treatments.
  6. ECOG performance status of 0 or 1.
  7. Adequate hematologic and renal function, based upon meeting protocol defined laboratory criteria within 7 days before randomization.
  8. Child-Pugh Score of A.
  9. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection.
  10. Sexually active fertile subjects(male and female)must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment.
  11. Female subjects of childbearing potential must not be pregnant at screening.

Select Exclusion Criteria:

  1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma.
  2. Receipt of more than 2 prior systemic therapies for advanced HCC.
  3. Any type of anticancer agent (including investigational) within 2 weeks before randomization.
  4. Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment within 6 weeks of randomization.
  5. Prior cabozantinib treatment.
  6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before randomization.
  7. Concomitant anticoagulation, at therapeutic doses, with anticoagulants.
  8. Serious illness other than cancer that would preclude safe participation in the study.
  9. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding.
  10. Moderate or severe ascites.
  11. Pregnant or lactating females.
  12. Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cabozantinib (XL184)

Placebo

Arm Description

Cabozantinib (XL184) 60 mg tablet once daily

Oral cabozantinib-matched placebo tablet once daily

Outcomes

Primary Outcome Measures

Overall Survival (OS)
The primary analysis of OS is defined as the time from randomization to death from any cause. The analysis was based on a second planned interim analysis prespecified to be performed at approximately the 75% information fraction (ie, at approximately 466 deaths). The data cutoff date for this event-driven analysis in the Intent to Treat (ITT) population was 01 June 2017. Median OS was calculated using the Kaplan-Meier estimates.

Secondary Outcome Measures

Progression-Free Survival (PFS)
Duration of PFS is defined as the time of randomization to the earlier of the following events, progressive disease as determined by Investigator (per RECIST 1.0, which is defined by a ≥ 20% increase in the sum of the longest diameter of target lesions from baseline) or death due to any cause. A Kaplan- Meier analysis was performed to estimate the median duration.
Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Full Information

First Posted
July 23, 2013
Last Updated
April 8, 2021
Sponsor
Exelixis
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1. Study Identification

Unique Protocol Identification Number
NCT01908426
Brief Title
Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
Acronym
CELESTIAL
Official Title
A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
September 26, 2013 (undefined)
Primary Completion Date
October 16, 2017 (Actual)
Study Completion Date
January 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Exelixis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the effect of Cabozantinib (XL184) compared with placebo on overall survival in subjects with advanced hepatocellular carcinoma who have received prior sorafenib.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
cabozantinib, XL184, liver cancer, hepatocellular carcinoma, tyrosine kinase inhibitor, MET kinase, vascular endothelial growth factor receptor 2 (VEGFR2)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
707 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cabozantinib (XL184)
Arm Type
Experimental
Arm Description
Cabozantinib (XL184) 60 mg tablet once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral cabozantinib-matched placebo tablet once daily
Intervention Type
Drug
Intervention Name(s)
Cabozantinib tablets
Other Intervention Name(s)
XL184
Intervention Type
Drug
Intervention Name(s)
Placebo tablets
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
The primary analysis of OS is defined as the time from randomization to death from any cause. The analysis was based on a second planned interim analysis prespecified to be performed at approximately the 75% information fraction (ie, at approximately 466 deaths). The data cutoff date for this event-driven analysis in the Intent to Treat (ITT) population was 01 June 2017. Median OS was calculated using the Kaplan-Meier estimates.
Time Frame
Up to 45 months
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
Duration of PFS is defined as the time of randomization to the earlier of the following events, progressive disease as determined by Investigator (per RECIST 1.0, which is defined by a ≥ 20% increase in the sum of the longest diameter of target lesions from baseline) or death due to any cause. A Kaplan- Meier analysis was performed to estimate the median duration.
Time Frame
Up to 45 months
Title
Objective Response Rate (ORR)
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame
ORR is measured by radiologic assessment every 8 weeks after randomization until disease progression or discontinuation of study treatment (up to 45 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Select Inclusion Criteria: Histological or cytological diagnosis of HCC. The subject has disease that is not amenable to a curative treatment approach. Received prior sorafenib. Progression following at least 1 prior systemic treatment for HCC. Recovery to from toxicities related to any prior treatments. ECOG performance status of 0 or 1. Adequate hematologic and renal function, based upon meeting protocol defined laboratory criteria within 7 days before randomization. Child-Pugh Score of A. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection. Sexually active fertile subjects(male and female)must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment. Female subjects of childbearing potential must not be pregnant at screening. Select Exclusion Criteria: Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma. Receipt of more than 2 prior systemic therapies for advanced HCC. Any type of anticancer agent (including investigational) within 2 weeks before randomization. Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment within 6 weeks of randomization. Prior cabozantinib treatment. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before randomization. Concomitant anticoagulation, at therapeutic doses, with anticoagulants. Serious illness other than cancer that would preclude safe participation in the study. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding. Moderate or severe ascites. Pregnant or lactating females. Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors.
Facility Information:
City
Corona
State/Province
California
ZIP/Postal Code
92879
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96815
Country
United States
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
City
Burlington
State/Province
Massachusetts
ZIP/Postal Code
01805
Country
United States
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64128
Country
United States
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
City
East Orange
State/Province
New Jersey
ZIP/Postal Code
07018
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
City
Spokane
State/Province
Washington
ZIP/Postal Code
99208
Country
United States
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
City
Concord
State/Province
New South Wales
ZIP/Postal Code
2139
Country
Australia
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
City
Kurralta Park
State/Province
South Australia
ZIP/Postal Code
5037
Country
Australia
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
City
Edegem
State/Province
Antwerpen
ZIP/Postal Code
2650
Country
Belgium
City
La Louvière
State/Province
Hainaut
ZIP/Postal Code
7100
Country
Belgium
City
Gent
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada
City
Nice
State/Province
Alpes-Maritimes
ZIP/Postal Code
6202
Country
France
City
Amiens
State/Province
Somme
ZIP/Postal Code
80054
Country
France
City
Creteil
State/Province
Val-de-Marne
ZIP/Postal Code
94010
Country
France
City
Besançon
ZIP/Postal Code
25000
Country
France
City
Bordeaux
ZIP/Postal Code
33075
Country
France
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
City
Lille
ZIP/Postal Code
59037
Country
France
City
Lyon
ZIP/Postal Code
69317
Country
France
City
Esslingen am Neckar
State/Province
Baden-Württemberg
ZIP/Postal Code
73730
Country
Germany
City
Tübingen
State/Province
Baden-Württemberg
ZIP/Postal Code
72076
Country
Germany
City
München
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
City
Frankfurt am Main
State/Province
Hessen
ZIP/Postal Code
60590
Country
Germany
City
Magdeburg
State/Province
Sachsen-Anhalt
ZIP/Postal Code
39120
Country
Germany
City
Berlin
ZIP/Postal Code
13353
Country
Germany
City
Freiburg
Country
Germany
City
Hong Kong
Country
Hong Kong
City
Dublin
ZIP/Postal Code
7
Country
Ireland
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
City
Faenza
State/Province
Emilia-Romagna
ZIP/Postal Code
48018
Country
Italy
City
Meldola
State/Province
Emilia-Romagna
ZIP/Postal Code
47014
Country
Italy
City
Rimini
State/Province
Emilia-Romagna
ZIP/Postal Code
47900
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
128
Country
Italy
City
Roma
State/Province
Lazio
ZIP/Postal Code
168
Country
Italy
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
City
Milan
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
City
Rozzano
State/Province
Lombardia
ZIP/Postal Code
20089
Country
Italy
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
City
Goyang
State/Province
Gyeonggido
ZIP/Postal Code
410-769
Country
Korea, Republic of
City
Busan
ZIP/Postal Code
602-739
Country
Korea, Republic of
City
Seongnam
ZIP/Postal Code
463-707
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
136-705
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
137-701
Country
Korea, Republic of
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
City
Suwon-si
ZIP/Postal Code
443-721
Country
Korea, Republic of
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6229 HX
Country
Netherlands
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1081 HV
Country
Netherlands
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
City
Leiden
State/Province
Zuid-Holland
ZIP/Postal Code
2333 ZA
Country
Netherlands
City
Auckland
State/Province
North Island
ZIP/Postal Code
1003
Country
New Zealand
City
Olsztyn
State/Province
Warminsko-Mazurskie
ZIP/Postal Code
10-513
Country
Poland
City
Myslowice
ZIP/Postal Code
41-400
Country
Poland
City
Poznan
ZIP/Postal Code
60-569
Country
Poland
City
Cluj-Napoca
State/Province
Cluj
ZIP/Postal Code
400015
Country
Romania
City
Brasov
ZIP/Postal Code
500019
Country
Romania
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
City
Singapore
ZIP/Postal Code
308433
Country
Singapore
City
Elche
State/Province
Alicante
ZIP/Postal Code
3293
Country
Spain
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
City
Torrejon de Ardoz
State/Province
Madrid
ZIP/Postal Code
28850
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28041
Country
Spain
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
City
Liuying Township
State/Province
Tainan
ZIP/Postal Code
736
Country
Taiwan
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
City
Edirne
ZIP/Postal Code
22030
Country
Turkey
City
Gaziantep
ZIP/Postal Code
27100
Country
Turkey
City
Wirral
State/Province
England
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35487183
Citation
Freemantle N, Mollon P, Meyer T, Cheng AL, El-Khoueiry AB, Kelley RK, Baron AD, Benzaghou F, Mangeshkar M, Abou-Alfa GK. Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial. Eur J Cancer. 2022 Jun;168:91-98. doi: 10.1016/j.ejca.2022.03.021. Epub 2022 Apr 26.
Results Reference
derived
PubMed Identifier
35397508
Citation
El-Khoueiry AB, Meyer T, Cheng AL, Rimassa L, Sen S, Milwee S, Kelley RK, Abou-Alfa GK. Safety and efficacy of cabozantinib for patients with advanced hepatocellular carcinoma who advanced to Child-Pugh B liver function at study week 8: a retrospective analysis of the CELESTIAL randomised controlled trial. BMC Cancer. 2022 Apr 9;22(1):377. doi: 10.1186/s12885-022-09453-z.
Results Reference
derived
PubMed Identifier
34621044
Citation
Kelley RK, Miksad R, Cicin I, Chen Y, Klumpen HJ, Kim S, Lin ZZ, Youkstetter J, Hazra S, Sen S, Cheng AL, El-Khoueiry AB, Meyer T, Abou-Alfa GK. Efficacy and safety of cabozantinib for patients with advanced hepatocellular carcinoma based on albumin-bilirubin grade. Br J Cancer. 2022 Mar;126(4):569-575. doi: 10.1038/s41416-021-01532-5. Epub 2021 Oct 7.
Results Reference
derived
PubMed Identifier
33822328
Citation
Trojan J, Mollon P, Daniele B, Marteau F, Martin L, Li Y, Xu Q, Piscaglia F, Zaucha R, Sarker D, Lim HY, Venerito M. Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein >/= 400 ng/mL: A Matching-Adjusted Indirect Comparison. Adv Ther. 2021 May;38(5):2472-2490. doi: 10.1007/s12325-021-01700-2. Epub 2021 Apr 6.
Results Reference
derived
PubMed Identifier
32847838
Citation
Kelley RK, Ryoo BY, Merle P, Park JW, Bolondi L, Chan SL, Lim HY, Baron AD, Parnis F, Knox J, Cattan S, Yau T, Lougheed JC, Milwee S, El-Khoueiry AB, Cheng AL, Meyer T, Abou-Alfa GK. Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial. ESMO Open. 2020 Aug;5(4):e000714. doi: 10.1136/esmoopen-2020-000714.
Results Reference
derived
PubMed Identifier
29972759
Citation
Abou-Alfa GK, Meyer T, Cheng AL, El-Khoueiry AB, Rimassa L, Ryoo BY, Cicin I, Merle P, Chen Y, Park JW, Blanc JF, Bolondi L, Klumpen HJ, Chan SL, Zagonel V, Pressiani T, Ryu MH, Venook AP, Hessel C, Borgman-Hagey AE, Schwab G, Kelley RK. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018 Jul 5;379(1):54-63. doi: 10.1056/NEJMoa1717002.
Results Reference
derived

Learn more about this trial

Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib

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