Clinical trial NCT01908426: Study of Cabozantinib (XL184) vs Placebo in Subjects With Hepatocellular Carcinoma Who Have Received Prior Sorafenib
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatocellular Carcinoma
Keywords: cabozantinib
XL184
liver cancer
hepatocellular carcinoma
tyrosine kinase inhibitor
MET kinase
vascular endothelial growth factor receptor 2 (VEGFR2)
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2013-07-25
Enrollment: 707
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 45 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to 45 months
measure: Objective Response Rate (ORR)
timeFrame: ORR is measured by radiologic assessment every 8 weeks after randomization until disease progression or discontinuation of study treatment (up to 45 months)
Other outcomes:
Locations:
city: Corona
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Honolulu
country: United States
state: Hawaii
city: Chicago
country: United States
state: Illinois
city: Burlington
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: East Orange
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Dallas
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Camperdown
country: Australia
state: New South Wales
city: Concord
country: Australia
state: New South Wales
city: Darlinghurst
country: Australia
state: New South Wales
city: Kogarah
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: Kurralta Park
country: Australia
state: South Australia
city: Melbourne
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Edegem
country: Belgium
state: Antwerpen
city: La Louvière
country: Belgium
state: Hainaut
city: Gent
country: Belgium
state: Oost-Vlaanderen
city: Liege
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Saskatoon
country: Canada
state: Saskatchewan
city: Nice
country: France
state: Alpes-Maritimes
city: Amiens
country: France
state: Somme
city: Creteil
country: France
state: Val-de-Marne
city: Besançon
country: France
city: Bordeaux
country: France
city: Clermont-Ferrand
country: France
city: Lille
country: France
city: Lyon
country: France
city: Esslingen am Neckar
country: Germany
state: Baden-Württemberg
city: Tübingen
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Frankfurt am Main
country: Germany
state: Hessen
city: Magdeburg
country: Germany
state: Sachsen-Anhalt
city: Berlin
country: Germany
city: Freiburg
country: Germany
city: Hong Kong
country: Hong Kong
city: Dublin
country: Ireland
city: Bologna
country: Italy
state: Emilia-Romagna
city: Faenza
country: Italy
state: Emilia-Romagna
city: Meldola
country: Italy
state: Emilia-Romagna
city: Rimini
country: Italy
state: Emilia-Romagna
city: Roma
country: Italy
state: Lazio
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Milan
country: Italy
state: Lombardia
city: Rozzano
country: Italy
state: Lombardia
city: Palermo
country: Italy
state: Sicilia
city: Padova
country: Italy
state: Veneto
city: Goyang
country: Korea, Republic of
state: Gyeonggido
city: Busan
country: Korea, Republic of
city: Seongnam
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon-si
country: Korea, Republic of
city: Maastricht
country: Netherlands
state: Limburg
city: Amsterdam
country: Netherlands
state: Noord-Holland
city: Amsterdam
country: Netherlands
state: Noord-Holland
city: Leiden
country: Netherlands
state: Zuid-Holland
city: Auckland
country: New Zealand
state: North Island
city: Olsztyn
country: Poland
state: Warminsko-Mazurskie
city: Myslowice
country: Poland
city: Poznan
country: Poland
city: Cluj-Napoca
country: Romania
state: Cluj
city: Brasov
country: Romania
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Elche
country: Spain
state: Alicante
city: Majadahonda
country: Spain
state: Madrid
city: Torrejon de Ardoz
country: Spain
state: Madrid
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Zaragoza
country: Spain
city: Liuying Township
country: Taiwan
state: Tainan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Edirne
country: Turkey
city: Gaziantep
country: Turkey
city: Wirral
country: United Kingdom
state: England
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.