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Hepatocellular CarcinomaPhase 3CELESTIALNCT01908426

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

A Phase 3 study testing Cabozantinib tablets in people with Hepatocellular Carcinoma, run by Exelixis at 104 sites in 19 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Cabozantinib tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
707 participants
Where
104 sitesin 19 countries
Study dates
26 Sep 2013to 12 Jan 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

104 sites in 19 countries.

104 sites in 19 countries

United States22 sites

  • Study site

    Atlanta, Georgia, 30318

  • Study site

    Burlington, Massachusetts, 01805

  • Study site

    Chicago, Illinois, 60637

  • Study site

    Corona, California, 92879

  • Study site

    Dallas, Texas, 75246

  • Study site

    East Orange, New Jersey, 07018

  • Study site

    Gainesville, Florida, 32610

  • Study site

    Honolulu, Hawaii, 96815

  • Study site

    Kansas City, Missouri, 64128

  • Study site

    Las Vegas, Nevada, 89109

  • Study site

    Los Angeles, California, 90033

  • Study site

    New York, New York, 10032

  • Study site

    New York, New York, 10065

  • Study site

    Rochester, Minnesota, 55905

  • Study site

    San Antonio, Texas, 78215

  • Study site

    San Diego, California, 92123

  • Study site

    San Francisco, California, 94115

  • Study site

    Seattle, Washington, 98104

  • Study site

    Seattle, Washington, 98109

  • Study site

    Spokane, Washington, 99208

  • Study site

    St Louis, Missouri, 63110

  • Study site

    Valhalla, New York, 10595

Other trials in United States

Italy11 sites

  • Study site

    Bologna, Emilia-Romagna, 40138

  • Study site

    Faenza, Emilia-Romagna, 48018

  • Study site

    Genoa, Liguria, 16132

  • Study site

    Meldola, Emilia-Romagna, 47014

  • Study site

    Milan, Lombardy, 20122

  • Study site

    Padova, Veneto, 35128

  • Study site

    Palermo, Sicily, 90127

  • Study site

    Rimini, Emilia-Romagna, 47900

  • Study site

    Rome, Lazio, 128

  • Study site

    Rome, Lazio, 168

  • Study site

    Rozzano, Lombardy, 20089

Other trials in Italy

South Korea10 sites

  • Study site

    Busan, 602-739

  • Study site

    Goyang, Gyeonggido, 410-769

  • Study site

    Seongnam, 463-707

  • Study site

    Seoul, 110-744

  • Study site

    Seoul, 120-752

  • Study site

    Seoul, 135-710

  • Study site

    Seoul, 136-705

  • Study site

    Seoul, 137-701

  • Study site

    Seoul, 138-736

  • Study site

    Suwon, 443-721

Other trials in South Korea

Australia8 sites

  • Study site

    Camperdown, New South Wales, 2050

  • Study site

    Concord, New South Wales, 2139

  • Study site

    Darlinghurst, New South Wales, 2010

  • Study site

    Kogarah, New South Wales, 2217

  • Study site

    Kurralta Park, South Australia, 5037

  • Study site

    Melbourne, Victoria, 3050

  • Study site

    Perth, Western Australia, 6000

  • Study site

    Westmead, New South Wales, 2145

Other trials in Australia

France8 sites

  • Study site

    Amiens, Somme, 80054

  • Study site

    Besançon, 25000

  • Study site

    Bordeaux, 33075

  • Study site

    Clermont-Ferrand, 63003

  • Study site

    Créteil, Val-de-Marne, 94010

  • Study site

    Lille, 59037

  • Study site

    Lyon, 69317

  • Study site

    Nice, Alpes-Maritimes, 6202

Other trials in France

Germany7 sites

  • Study site

    Berlin, 13353

  • Study site

    Esslingen am Neckar, Baden-Wurttemberg, 73730

  • Study site

    Frankfurt am Main, Hesse, 60590

  • Study site

    Freiburg im Breisgau

  • Study site

    Magdeburg, Saxony-Anhalt, 39120

  • Study site

    München, Bavaria, 81675

  • Study site

    Tübingen, Baden-Wurttemberg, 72076

Other trials in Germany

Spain6 sites

  • Study site

    Elche, Alicante, 3293

  • Study site

    Madrid, 28007

  • Study site

    Madrid, 28041

  • Study site

    Majadahonda, Madrid, 28222

  • Study site

    Torrejón de Ardoz, Madrid, 28850

  • Study site

    Zaragoza, 50009

Other trials in Spain

United Kingdom5 sites

  • Study site

    Birmingham, B15 2TH

  • Study site

    London, NW3 2QG

  • Study site

    London, SE5 9RS

  • Study site

    Manchester, M20 4BX

  • Study site

    Metropolitan Borough of Wirral, England, CH63 4JY

Other trials in United Kingdom

Belgium4 sites

  • Study site

    Edegem, Antwerpen, 2650

  • Study site

    Ghent, Oost-Vlaanderen, 9000

  • Study site

    La Louvière, Hainaut, 7100

  • Study site

    Liège, 4000

Other trials in Belgium

Netherlands4 sites

  • Study site

    Amsterdam, North Holland, 1081 HV

  • Study site

    Amsterdam, North Holland, 1105 AZ

  • Study site

    Leiden, South Holland, 2333 ZA

  • Study site

    Maastricht, Limburg, 6229 HX

Other trials in Netherlands

Canada3 sites

  • Study site

    Calgary, Alberta, T2N 4N2

  • Study site

    Saskatoon, Saskatchewan, S7N 4H4

  • Study site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Poland3 sites

  • Study site

    Mysłowice, 41-400

  • Study site

    Olsztyn, Warmian-Masurian Voivodeship, 10-513

  • Study site

    Poznan, 60-569

Other trials in Poland

Singapore3 sites

  • Study site

    Singapore, 119074

  • Study site

    Singapore, 169610

  • Study site

    Singapore, 308433

Other trials in Singapore

Taiwan3 sites

  • Study site

    Liuying Township, Tainan, 736

  • Study site

    Taichung, 40705

  • Study site

    Taipei, 100

Other trials in Taiwan

Romania2 sites

  • Study site

    Brasov, 500019

  • Study site

    Cluj-Napoca, Cluj, 400015

Other trials in Romania

Turkey (Türkiye)2 sites

  • Study site

    Edirne, 22030

  • Study site

    Gaziantep, 27100

Other trials in Turkey (Türkiye)

Hong Kong1 site

  • Study site

    Hong Kong

Other trials in Hong Kong

Ireland1 site

  • Study site

    Dublin, 7

Other trials in Ireland

New Zealand1 site

  • Study site

    Auckland, North Island, 1003

Other trials in New Zealand

About this study

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

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.

Being tested
Cabozantinib tablets, Placebo tablets
Keywords
cabozantinib, XL184, liver cancer, hepatocellular carcinoma, tyrosine kinase inhibitor, MET kinase, vascular endothelial growth factor receptor 2 (VEGFR2)
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cabozantinib tabletsDrug

    Also called XL184

  • Placebo tabletsDrug

Study groups in NCT01908426
Study groupRoleWhat they receive
Cabozantinib (XL184)ExperimentalCabozantinib (XL184) 60 mg tablet once daily
Receives: Drug: Cabozantinib tablets
PlaceboPlacebo comparatorOral cabozantinib-matched placebo tablet once daily
Receives: Drug: Placebo tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 45 months

Secondary outcomes (2)

  1. 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.

    Measured: Up to 45 months

  2. 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.

    Measured: ORR is measured by radiologic assessment every 8 weeks after randomization until disease progression or discontinuation of study treatment (up to 45 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jul 2013 (estimated)
  2. Study start26 Sep 2013
  3. Primary completion16 Oct 2017
  4. Study completion12 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
707 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01908426
Sponsor's protocol ID
XL184-309
Acronym
CELESTIAL
Status last verified
Apr 2021
First submitted
23 Jul 2013
Last updated
6 May 2021
Data monitoring committee
Yes

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.

    PubMed 35487183

  • 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.

    PubMed 35397508

  • 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.

    PubMed 34621044

  • 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.

    PubMed 33822328

  • 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.

    PubMed 32847838

  • 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.

    PubMed 29972759

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cabozantinib tablets in people with Hepatocellular Carcinoma, run by Exelixis at 104 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 104 sites in United States, Italy, South Korea, Australia, France and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Up to 45 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01908426, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.

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