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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01908426
Recruitment Status : Active, not recruiting
First Posted : July 25, 2013
Results First Posted : March 1, 2019
Last Update Posted : March 1, 2019
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: Cabozantinib tablets Drug: Placebo tablets Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 707 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : September 26, 2013
Actual Primary Completion Date : October 16, 2017
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Cabozantinib (XL184)
Cabozantinib (XL184) 60 mg tablet once daily
Drug: Cabozantinib tablets
Other Name: XL184

Placebo Comparator: Placebo
Oral cabozantinib-matched placebo tablet once daily
Drug: Placebo tablets

Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 45 months ]
    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 :
  1. Progression-Free Survival (PFS) [ Time Frame: Up to 45 months ]
    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.

  2. Objective Response Rate (ORR) [ 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) ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01908426

  Hide Study Locations
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United States, California
Corona, California, United States, 92879
Los Angeles, California, United States, 90033
San Diego, California, United States, 92123
San Francisco, California, United States, 94115
United States, Florida
Gainesville, Florida, United States, 32610
United States, Georgia
Atlanta, Georgia, United States, 30318
United States, Hawaii
Honolulu, Hawaii, United States, 96815
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Massachusetts
Burlington, Massachusetts, United States, 01805
United States, Minnesota
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City, Missouri, United States, 64128
Saint Louis, Missouri, United States, 63110
United States, Nevada
Las Vegas, Nevada, United States, 89109
United States, New Jersey
East Orange, New Jersey, United States, 07018
United States, New York
New York, New York, United States, 10032
New York, New York, United States, 10065
Valhalla, New York, United States, 10595
United States, Texas
Dallas, Texas, United States, 75246
San Antonio, Texas, United States, 78215
United States, Washington
Seattle, Washington, United States, 98104
Seattle, Washington, United States, 98109
Spokane, Washington, United States, 99208
Australia, New South Wales
Camperdown, New South Wales, Australia, 2050
Concord, New South Wales, Australia, 2139
Darlinghurst, New South Wales, Australia, 2010
Kogarah, New South Wales, Australia, 2217
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Kurralta Park, South Australia, Australia, 5037
Australia, Victoria
Melbourne, Victoria, Australia, 3050
Australia, Western Australia
Perth, Western Australia, Australia, 6000
Edegem, Antwerpen, Belgium, 2650
La Louvière, Hainaut, Belgium, 7100
Gent, Oost-Vlaanderen, Belgium, 9000
Liege, Belgium, 4000
Canada, Alberta
Calgary, Alberta, Canada, T2N 4N2
Canada, Ontario
Toronto, Ontario, Canada, M5G 2M9
Canada, Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Nice, Alpes-Maritimes, France, 6202
Amiens, Somme, France, 80054
Creteil, Val-de-Marne, France, 94010
Besançon, France, 25000
Bordeaux, France, 33075
Clermont-Ferrand, France, 63003
Lille, France, 59037
Lyon, France, 69317
Esslingen am Neckar, Baden-Württemberg, Germany, 73730
Tübingen, Baden-Württemberg, Germany, 72076
München, Bayern, Germany, 81675
Frankfurt am Main, Hessen, Germany, 60590
Magdeburg, Sachsen-Anhalt, Germany, 39120
Berlin, Germany, 13353
Freiburg, Germany
Hong Kong
Hong Kong, Hong Kong
Dublin, Ireland, 7
Bologna, Emilia-Romagna, Italy, 40138
Faenza, Emilia-Romagna, Italy, 48018
Meldola, Emilia-Romagna, Italy, 47014
Rimini, Emilia-Romagna, Italy, 47900
Roma, Lazio, Italy, 128
Roma, Lazio, Italy, 168
Genova, Liguria, Italy, 16132
Milan, Lombardia, Italy, 20122
Rozzano, Lombardia, Italy, 20089
Palermo, Sicilia, Italy, 90127
Padova, Veneto, Italy, 35128
Korea, Republic of
Goyang, Gyeonggido, Korea, Republic of, 410-769
Busan, Korea, Republic of, 602-739
Seongnam, Korea, Republic of, 463-707
Seoul, Korea, Republic of, 110-744
Seoul, Korea, Republic of, 120-752
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 136-705
Seoul, Korea, Republic of, 137-701
Seoul, Korea, Republic of, 138-736
Suwon-si, Korea, Republic of, 443-721
Maastricht, Limburg, Netherlands, 6229 HX
Amsterdam, Noord-Holland, Netherlands, 1081 HV
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Leiden, Zuid-Holland, Netherlands, 2333 ZA
New Zealand
Auckland, North Island, New Zealand, 1003
Olsztyn, Warminsko-Mazurskie, Poland, 10-513
Myslowice, Poland, 41-400
Poznan, Poland, 60-569
Cluj-Napoca, Cluj, Romania, 400015
Brasov, Romania, 500019
Singapore, Singapore, 119074
Singapore, Singapore, 169610
Singapore, Singapore, 308433
Elche, Alicante, Spain, 3293
Majadahonda, Madrid, Spain, 28222
Torrejon de Ardoz, Madrid, Spain, 28850
Madrid, Spain, 28007
Madrid, Spain, 28041
Zaragoza, Spain, 50009
Liuying Township, Tainan, Taiwan, 736
Taichung, Taiwan, 40705
Taipei, Taiwan, 100
Edirne, Turkey, 22030
Gaziantep, Turkey, 27100
United Kingdom
Wirral, England, United Kingdom, CH63 4JY
Birmingham, United Kingdom, B15 2TH
London, United Kingdom, NW3 2QG
London, United Kingdom, SE5 9RS
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
  Study Documents (Full-Text)

Documents provided by Exelixis:
Study Protocol  [PDF] July 12, 2016
Statistical Analysis Plan  [PDF] June 8, 2016

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Exelixis Identifier: NCT01908426     History of Changes
Other Study ID Numbers: XL184-309
First Posted: July 25, 2013    Key Record Dates
Results First Posted: March 1, 2019
Last Update Posted: March 1, 2019
Last Verified: February 2019

Keywords provided by Exelixis:
liver cancer
hepatocellular carcinoma
tyrosine kinase inhibitor
MET kinase
vascular endothelial growth factor receptor 2 (VEGFR2)

Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action