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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01908426




Registration number
NCT01908426
Ethics application status
Date submitted
23/07/2013
Date registered
25/07/2013
Date last updated
6/05/2021

Titles & IDs
Public title
Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
Scientific title
A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
Secondary ID [1] 0 0
XL184-309
Universal Trial Number (UTN)
Trial acronym
CELESTIAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Cabozantinib (XL184) - Cabozantinib (XL184) 60 mg tablet once daily

Placebo comparator: Placebo - Oral cabozantinib-matched placebo tablet once daily
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to 45 months
Secondary outcome [1] 0 0
Progression-Free Survival (PFS)
Timepoint [1] 0 0
Up to 45 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
ORR is measured by radiologic assessment every 8 weeks after randomization until disease progression or discontinuation of study treatment (up to 45 months)

Eligibility
Key inclusion criteria
Select

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
12/01/2021
Sample size
Target
Accrual to date
Final
707
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Concord
Recruitment hospital [3] 0 0
- Darlinghurst
Recruitment hospital [4] 0 0
- Kogarah
Recruitment hospital [5] 0 0
- Westmead
Recruitment hospital [6] 0 0
- Kurralta Park
Recruitment hospital [7] 0 0
- Melbourne
Recruitment hospital [8] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [7] 0 0
3050 - Melbourne
Recruitment postcode(s) [8] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Florida
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United States of America
State/province [3] 0 0
Georgia
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United States of America
State/province [4] 0 0
Hawaii
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United States of America
State/province [5] 0 0
Illinois
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United States of America
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Massachusetts
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United States of America
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Minnesota
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United States of America
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Missouri
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Nevada
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New Jersey
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United States of America
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New York
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United States of America
State/province [12] 0 0
Texas
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United States of America
State/province [13] 0 0
Washington
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Belgium
State/province [14] 0 0
Antwerpen
Country [15] 0 0
Belgium
State/province [15] 0 0
Hainaut
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Belgium
State/province [16] 0 0
Oost-Vlaanderen
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Belgium
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Liege
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Canada
State/province [18] 0 0
Alberta
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Canada
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Ontario
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Canada
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Saskatchewan
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France
State/province [21] 0 0
Alpes-Maritimes
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France
State/province [22] 0 0
Somme
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France
State/province [23] 0 0
Val-de-Marne
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France
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Besançon
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France
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Bordeaux
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France
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Clermont-Ferrand
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France
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Lille
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France
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Lyon
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Germany
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Baden-Württemberg
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Germany
State/province [30] 0 0
Bayern
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Germany
State/province [31] 0 0
Hessen
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Germany
State/province [32] 0 0
Sachsen-Anhalt
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
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Germany
State/province [34] 0 0
Freiburg
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Hong Kong
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Hong Kong
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Ireland
State/province [36] 0 0
Dublin
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Italy
State/province [37] 0 0
Emilia-Romagna
Country [38] 0 0
Italy
State/province [38] 0 0
Lazio
Country [39] 0 0
Italy
State/province [39] 0 0
Liguria
Country [40] 0 0
Italy
State/province [40] 0 0
Lombardia
Country [41] 0 0
Italy
State/province [41] 0 0
Sicilia
Country [42] 0 0
Italy
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Veneto
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Korea, Republic of
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Gyeonggido
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Korea, Republic of
State/province [44] 0 0
Busan
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Korea, Republic of
State/province [45] 0 0
Seongnam
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Korea, Republic of
State/province [46] 0 0
Seoul
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Korea, Republic of
State/province [47] 0 0
Suwon-si
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Netherlands
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Limburg
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Netherlands
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Noord-Holland
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Netherlands
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Zuid-Holland
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New Zealand
State/province [51] 0 0
North Island
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Poland
State/province [52] 0 0
Warminsko-Mazurskie
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Poland
State/province [53] 0 0
Myslowice
Country [54] 0 0
Poland
State/province [54] 0 0
Poznan
Country [55] 0 0
Romania
State/province [55] 0 0
Cluj
Country [56] 0 0
Romania
State/province [56] 0 0
Brasov
Country [57] 0 0
Singapore
State/province [57] 0 0
Singapore
Country [58] 0 0
Spain
State/province [58] 0 0
Alicante
Country [59] 0 0
Spain
State/province [59] 0 0
Madrid
Country [60] 0 0
Spain
State/province [60] 0 0
Zaragoza
Country [61] 0 0
Taiwan
State/province [61] 0 0
Tainan
Country [62] 0 0
Taiwan
State/province [62] 0 0
Taichung
Country [63] 0 0
Taiwan
State/province [63] 0 0
Taipei
Country [64] 0 0
Turkey
State/province [64] 0 0
Edirne
Country [65] 0 0
Turkey
State/province [65] 0 0
Gaziantep
Country [66] 0 0
United Kingdom
State/province [66] 0 0
England
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Birmingham
Country [68] 0 0
United Kingdom
State/province [68] 0 0
London
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Exelixis
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01908426
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01908426