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

NCT01908426 | Completed Phase 3 Results DMC

• 1 other identifier: XL184-309
• Study Type: interventional
• Target: 707
• Locations: 19 countries
• Sites: 104

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.

Conditions

Hepatocellular Carcinoma

Keywords

cabozantinib; XL184; liver cancer; hepatocellular carcinoma; tyrosine kinase inhibitor; MET kinase; vascular endothelial growth factor receptor 2 (VEGFR2)

Outcome Measures

Primary Outcomes (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.

  Up to 45 months

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  Up to 45 months

• Objective Response Rate (ORR)

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

Study Arms (2)

Cabozantinib (XL184)

EXPERIMENTAL

Cabozantinib (XL184) 60 mg tablet once daily

Drug: Cabozantinib tablets

Placebo

PLACEBO COMPARATOR

Oral cabozantinib-matched placebo tablet once daily

Drug: Placebo tablets

Interventions

Cabozantinib tablets DRUG

Also known as: XL184

Cabozantinib (XL184)

Placebo tablets DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (104)

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Corona, California, 92879, United States

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Los Angeles, California, 90033, United States

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San Diego, California, 92123, United States

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San Francisco, California, 94115, United States

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Gainesville, Florida, 32610, United States

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Atlanta, Georgia, 30318, United States

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Honolulu, Hawaii, 96815, United States

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Chicago, Illinois, 60637, United States

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Burlington, Massachusetts, 01805, United States

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Rochester, Minnesota, 55905, United States

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Kansas City, Missouri, 64128, United States

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St Louis, Missouri, 63110, United States

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Las Vegas, Nevada, 89109, United States

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East Orange, New Jersey, 07018, United States

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New York, New York, 10032, United States

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New York, New York, 10065, United States

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Valhalla, New York, 10595, United States

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Dallas, Texas, 75246, United States

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San Antonio, Texas, 78215, United States

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Seattle, Washington, 98104, United States

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Seattle, Washington, 98109, United States

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Spokane, Washington, 99208, United States

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Camperdown, New South Wales, 2050, Australia

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Concord, New South Wales, 2139, Australia

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Darlinghurst, New South Wales, 2010, Australia

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Kogarah, New South Wales, 2217, Australia

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Westmead, New South Wales, 2145, Australia

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Kurralta Park, South Australia, 5037, Australia

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Melbourne, Victoria, 3050, Australia

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Perth, Western Australia, 6000, Australia

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Edegem, Antwerpen, 2650, Belgium

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La Louvière, Hainaut, 7100, Belgium

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Ghent, Oost-Vlaanderen, 9000, Belgium

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Liège, 4000, Belgium

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Calgary, Alberta, T2N 4N2, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Saskatoon, Saskatchewan, S7N 4H4, Canada

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Nice, Alpes-Maritimes, 6202, France

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Amiens, Somme, 80054, France

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Créteil, Val-de-Marne, 94010, France

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Besançon, 25000, France

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Bordeaux, 33075, France

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Clermont-Ferrand, 63003, France

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Lille, 59037, France

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Lyon, 69317, France

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Esslingen am Neckar, Baden-Wurttemberg, 73730, Germany

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Tübingen, Baden-Wurttemberg, 72076, Germany

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München, Bavaria, 81675, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Magdeburg, Saxony-Anhalt, 39120, Germany

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Berlin, 13353, Germany

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Freiburg im Breisgau, Germany

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Hong Kong, Hong Kong

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Dublin, 7, Ireland

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Bologna, Emilia-Romagna, 40138, Italy

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Faenza, Emilia-Romagna, 48018, Italy

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Meldola, Emilia-Romagna, 47014, Italy

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Rimini, Emilia-Romagna, 47900, Italy

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Rome, Lazio, 128, Italy

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Rome, Lazio, 168, Italy

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Genoa, Liguria, 16132, Italy

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Milan, Lombardy, 20122, Italy

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Rozzano, Lombardy, 20089, Italy

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Palermo, Sicily, 90127, Italy

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Padua, Veneto, 35128, Italy

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Maastricht, Limburg, 6229 HX, Netherlands

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Amsterdam, North Holland, 1081 HV, Netherlands

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Amsterdam, North Holland, 1105 AZ, Netherlands

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Leiden, South Holland, 2333 ZA, Netherlands

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Auckland, North Island, 1003, New Zealand

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Olsztyn, Warmian-Masurian Voivodeship, 10-513, Poland

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Mysłowice, 41-400, Poland

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Poznan, 60-569, Poland

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Cluj-Napoca, Cluj, 400015, Romania

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Brasov, 500019, Romania

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Singapore, 119074, Singapore

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Singapore, 169610, Singapore

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Singapore, 308433, Singapore

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Goyang, Gyeonggido, 410-769, South Korea

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Busan, 602-739, South Korea

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Seongnam, 463-707, South Korea

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

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Seoul, 135-710, South Korea

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Seoul, 136-705, South Korea

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Seoul, 137-701, South Korea

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Seoul, 138-736, South Korea

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Suwon, 443-721, South Korea

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Elche, Alicante, 3293, Spain

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Majadahonda, Madrid, 28222, Spain

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Torrejón de Ardoz, Madrid, 28850, Spain

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Madrid, 28007, Spain

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Madrid, 28041, Spain

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Zaragoza, 50009, Spain

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Liuying Township, Tainan, 736, Taiwan

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Taichung, 40705, Taiwan

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Taipei, 100, Taiwan

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Edirne, 22030, Turkey (Türkiye)

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Gaziantep, 27100, Turkey (Türkiye)

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Metropolitan Borough of Wirral, England, CH63 4JY, United Kingdom

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Birmingham, B15 2TH, United Kingdom

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London, NW3 2QG, United Kingdom

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London, SE5 9RS, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Related Publications (6)

• 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.

  PMID: 35487183 DERIVED

• 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.

  PMID: 35397508 DERIVED

• 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.

  PMID: 34621044 DERIVED

• 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.

  PMID: 33822328 DERIVED

• 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.

  PMID: 32847838 DERIVED

• 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.

  PMID: 29972759 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Exelixis Medical Information
• Organization: Exelixis, Inc.

druginfo@exelixis.com

855-292-3935

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2013
• First Posted: July 25, 2013
• Study Start: September 26, 2013
• Primary Completion: October 16, 2017
• Study Completion: January 12, 2021
• Last Updated: May 6, 2021
• Results First Posted: March 1, 2019

Record last verified: 2021-04

Locations

AU (8); CA (3); RO (2); IT (11); SG (3); HK (1); PL (3); DE (7); IE (1); TU (2); TW (3); BE (4); ES (6); US (22); NZ (1); FR (8); NL (4); KR (10); GB (5)