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

NCT ID: NCT01908426

Last Updated: 2021-05-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

707 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-26

Study Completion Date

2021-01-12

Brief Summary

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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.

Detailed Description

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Conditions

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Hepatocellular Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cabozantinib (XL184)

Cabozantinib (XL184) 60 mg tablet once daily

Group Type EXPERIMENTAL

Cabozantinib tablets

Intervention Type DRUG

Placebo

Oral cabozantinib-matched placebo tablet once daily

Group Type PLACEBO_COMPARATOR

Placebo tablets

Intervention Type DRUG

Interventions

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Cabozantinib tablets

Intervention Type DRUG

Placebo tablets

Intervention Type DRUG

Other Intervention Names

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XL184

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Corona, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Gainesville, Florida, United States

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Atlanta, Georgia, United States

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Honolulu, Hawaii, United States

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Chicago, Illinois, United States

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Burlington, Massachusetts, United States

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Rochester, Minnesota, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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East Orange, New Jersey, United States

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New York, New York, United States

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New York, New York, United States

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Valhalla, New York, United States

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Dallas, Texas, United States

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San Antonio, Texas, United States

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Seattle, Washington, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Camperdown, New South Wales, Australia

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Concord, New South Wales, Australia

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Darlinghurst, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Westmead, New South Wales, Australia

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Kurralta Park, South Australia, Australia

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Melbourne, Victoria, Australia

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Perth, Western Australia, Australia

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Edegem, Antwerpen, Belgium

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La Louvière, Hainaut, Belgium

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Ghent, Oost-Vlaanderen, Belgium

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Liège, , Belgium

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Calgary, Alberta, Canada

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Toronto, Ontario, Canada

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Saskatoon, Saskatchewan, Canada

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Nice, Alpes-Maritimes, France

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Amiens, Somme, France

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Créteil, Val-de-Marne, France

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Besançon, , France

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Bordeaux, , France

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Clermont-Ferrand, , France

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Lille, , France

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Lyon, , France

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Esslingen am Neckar, Baden-Wurttemberg, Germany

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Tübingen, Baden-Wurttemberg, Germany

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München, Bavaria, Germany

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Frankfurt am Main, Hesse, Germany

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Magdeburg, Saxony-Anhalt, Germany

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Berlin, , Germany

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Freiburg im Breisgau, , Germany

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Hong Kong, , Hong Kong

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Dublin, , Ireland

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Bologna, Emilia-Romagna, Italy

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Faenza, Emilia-Romagna, Italy

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Meldola, Emilia-Romagna, Italy

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Rimini, Emilia-Romagna, Italy

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Rome, Lazio, Italy

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Rome, Lazio, Italy

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Genoa, Liguria, Italy

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Milan, Lombardy, Italy

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Rozzano, Lombardy, Italy

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Palermo, Sicily, Italy

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Padua, Veneto, Italy

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Maastricht, Limburg, Netherlands

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Amsterdam, North Holland, Netherlands

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Amsterdam, North Holland, Netherlands

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Leiden, South Holland, Netherlands

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Auckland, North Island, New Zealand

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Olsztyn, Warmian-Masurian Voivodeship, Poland

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Mysłowice, , Poland

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Poznan, , Poland

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Cluj-Napoca, Cluj, Romania

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Brasov, , Romania

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Singapore, , Singapore

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Singapore, , Singapore

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Singapore, , Singapore

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Goyang, Gyeonggido, South Korea

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Busan, , South Korea

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Seongnam, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Elche, Alicante, Spain

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Majadahonda, Madrid, Spain

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Torrejón de Ardoz, Madrid, Spain

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Madrid, , Spain

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Madrid, , Spain

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Zaragoza, , Spain

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Liuying Township, Tainan, Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Edirne, , Turkey (Türkiye)

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Gaziantep, , Turkey (Türkiye)

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Metropolitan Borough of Wirral, England, United Kingdom

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Birmingham, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Countries

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United States Australia Belgium Canada France Germany Hong Kong Ireland Italy Netherlands New Zealand Poland Romania Singapore South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

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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.

Reference Type DERIVED
PMID: 35487183 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35397508 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34621044 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33822328 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32847838 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29972759 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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XL184-309

Identifier Type: -

Identifier Source: org_study_id

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