Study of Regorafenib After Sorafenib in Patients With Hepatocellular Carcinoma

NCT ID: NCT01774344

Last Updated: 2020-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 573 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-14
• Study Completion Date: 2019-07-05

Brief Summary

The objective of this study was to evaluate efficacy and safety of regorafenib in patients with advanced liver cancer who had progressed after sorafenib treatment. Patients were treated with regorafenib or placebo using a 2:1 randomization scheme.

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Regorafenib

160 mg orally (p.o.) every day (qd) for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC (Best Supportive Care)

Group Type: EXPERIMENTAL

Regorafenib (Stivarga, BAY73-4506)

Intervention Type: DRUG

Regorafenib, 40 mg tablets

Placebo

4 matching placebo tablets for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off) plus BSC

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets matching in appearance

Interventions

Regorafenib (Stivarga, BAY73-4506)

Regorafenib, 40 mg tablets

Intervention Type: DRUG

Placebo

Placebo tablets matching in appearance

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histological or cytological confirmation of HCC (hepatocellular carcinoma) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases criteria in patients with a confirmed diagnosis of cirrhosis
• Barcelona Clinic Liver Cancer stage Category B or C that cannot benefit from treatments of established efficacy with higher priority such as resection, local ablation, chemoembolization or systemic sorafenib.
• Failure to prior treatment with sorafenib (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 10 weeks after the last treatment with sorafenib.
• Tolerability of prior treatment with sorafenib defined as not less than 20 days at a minimum daily dose of 400 mg QD within the last 28 days prior to withdrawal.
• Liver function status Child-Pugh Class A. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period.

Local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >/=4 weeks before first dose of study medication. Note: patients who received sole intrahepatic intraarterial chemotherapy, without lipiodol or embolizing agents are not eligible.

• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted within 7 days before randomization.
• Glomerular filtration rate >/= 30 ml/min/1.73 m^2 according to the Modification of diet in renal disease study equation.
• At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST (RECIST version 1.1), and modified RECIST for HCC. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion.
• Life expectancy of at least 3 months.
• Women of childbearing potential and men must agree to use adequate contraception .

Exclusion Criteria

• Sorafenib treatment within 2 weeks of randomization.
• Prior systemic treatment for HCC, except sorafenib.
• Permanent discontinuation of prior sorafenib therapy due to sorafenib related toxicity.
• Known history or symptomatic metastatic brain or meningeal tumors (head CT or MRI at screening to confirm the absence of central nervous system [CNS] disease if patient has symptoms suggestive or consistent with CNS disease).
• Uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
• Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis treatment).
• Ongoing infection > Grade 2 according to NCI-CTCAE (National Cancer Institute - Common Terminology Criteria for Adverse Events) v. 4.0. Hepatitis B is allowed if no active replication is present. Hepatitis C is allowed if no antiviral treatment is required.
• Clinically significant bleeding NCI-CTCAE version 4.0 Grade 3 or higher within 30 days before randomization.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication.
• Patients unable to swallow oral medications.
• Interstitial lung disease with ongoing signs and symptoms at the time of screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Los Angeles, California, United States

Los Angeles, California, United States

Orange, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Gainesville, Florida, United States

Tampa, Florida, United States

Chicago, Illinois, United States

Louisville, Kentucky, United States

Worcester, Massachusetts, United States

Minneapolis, Minnesota, United States

St Louis, Missouri, United States

New York, New York, United States

Rochester, New York, United States

Pittsburgh, Pennsylvania, United States

Richmond, Virginia, United States

Seattle, Washington, United States

Pilar, Buenos Aires, Argentina

Camperdown, New South Wales, Australia

Liverpool, New South Wales, Australia

Herston, Queensland, Australia

Clayton, Victoria, Australia

Box Hill, , Australia

Graz, Styria, Austria

Linz, Upper Austria, Austria

Vienna, , Austria

Bruxelles - Brussel, , Belgium

La Louvière, , Belgium

Salvador, Estado de Bahia, Brazil

São Paulo, , Brazil

Hefei, Anhui, China

Fuzhou, Fujian, China

Guangzhou, Guangdong, China

Guangzhou, Guangdong, China

Guangzhou, Guangdong, China

Nanning, Guangxi, China

Harbin, Heilongjiang, China

Wuhan, Hubei, China

Changsha, Hunan, China

Nanjing, Jiangsu, China

Suzhou, Jiangsu, China

Dalian, Liaoning, China

Xi'an, Shaanxi, China

Xi'an, Shaanxi, China

Xi'an, Shaanxi, China

Chengdu, Sichuan, China

Beijing, , China

Beijing, , China

Beijing, , China

Beijing, , China

Chongqing, , China

Shanghai, , China

Shanghai, , China

Shanghai, , China

Tianjin, , China

Hradec Králové, , Czechia

Olomouc, , Czechia

Prague, , Czechia

Angers, , France

Caen, , France

Clichy, , France

Créteil, , France

Dijon, , France

La Tronche, , France

Lille, , France

Lyon, , France

Marseille, , France

Montpellier, , France

Nice, , France

Paris, , France

Paris, , France

Perpignan, , France

Reims, , France

Rennes, , France

Toulouse, , France

Vandœuvre-lès-Nancy, , France

Villejuif, , France

Heidelberg, Baden-Wurttemberg, Germany

München, Bavaria, Germany

Frankfurt am Main, Hesse, Germany

Hanover, Lower Saxony, Germany

Aachen, North Rhine-Westphalia, Germany

Cologne, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Mainz, Rhineland-Palatinate, Germany

Magdeburg, Saxony-Anhalt, Germany

Berlin, , Germany

Hamburg, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Kaposvár, , Hungary

Foggia, Apulia, Italy

Napoli, Campania, Italy

Bologna, Emilia-Romagna, Italy

Modena, Emilia-Romagna, Italy

Rome, Lazio, Italy

Genoa, Liguria, Italy

Bergamo, Lombardy, Italy

Milan, Lombardy, Italy

Milan, Lombardy, Italy

Novara, Piedmont, Italy

Turin, Piedmont, Italy

Cagliari, Sardinia, Italy

Pisa, Tuscany, Italy

Padua, Veneto, Italy

Chiba, Chiba, Japan

Kashiwa-shi, Chiba, Japan

Fukuoka, Fukuoka, Japan

Iizuka-shi, Fukuoka, Japan

Yokohama, Kanagawa, Japan

Kumamoto, Kumamoto, Japan

Osaka, Osaka, Japan

Osakasayama-shi, Osaka, Japan

Utsunomiya, Tochigi, Japan

Chiyoda-ku, Tokyo, Japan

Chuo-ku, Tokyo, Japan

Musashino-shi, Tokyo, Japan

Amsterdam, , Netherlands

Leiden, , Netherlands

Barnaul, , Russia

Moscow, , Russia

Moscow, , Russia

Singapore, , Singapore

Busan, Busan Gwang''yeogsi, South Korea

Daegu, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Oviedo, Principality of Asturias, Spain

Alicante, , Spain

Barcelona, , Spain

Barcelona, , Spain

Córdoba, , Spain

Madrid, , Spain

Madrid, , Spain

Madrid, , Spain

Zaragoza, , Spain

Bellinzona, Canton Ticino, Switzerland

Bern, , Switzerland

Kaohsiung City, Kaohsiung, Taiwan

Taipei, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Birmingham, West Midlands, United Kingdom

Leeds, West Yorkshire, United Kingdom

Bristol, , United Kingdom

London, , United Kingdom

London, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; China; Czechia; France; Germany; Hungary; Italy; Japan; Netherlands; Russia; Singapore; South Korea; Spain; Switzerland; Taiwan; United Kingdom

References

Finn RS, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Gerolami R, Caparello C, Cabrera R, Chang C, Sun W, LeBerre MA, Baumhauer A, Meinhardt G, Bruix J. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial. J Hepatol. 2018 Aug;69(2):353-358. doi: 10.1016/j.jhep.2018.04.010. Epub 2018 Apr 26.

Reference Type: RESULT

PMID: 29704513 (View on PubMed)

Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Jan 7;389(10064):56-66. doi: 10.1016/S0140-6736(16)32453-9. Epub 2016 Dec 6.

Reference Type: RESULT

PMID: 27932229 (View on PubMed)

Wu W, Mao H, Song J, Yang F. Bibliometric analysis of hepatocellular carcinoma and tyrosine kinase inhibitors. Medicine (Baltimore). 2025 May 16;104(20):e42015. doi: 10.1097/MD.0000000000042015.

Reference Type: DERIVED

PMID: 40388796 (View on PubMed)

Teufel M, Seidel H, Kochert K, Meinhardt G, Finn RS, Llovet JM, Bruix J. Biomarkers Associated With Response to Regorafenib in Patients With Hepatocellular Carcinoma. Gastroenterology. 2019 May;156(6):1731-1741. doi: 10.1053/j.gastro.2019.01.261. Epub 2019 Feb 6.

Reference Type: DERIVED

PMID: 30738047 (View on PubMed)

Related Links

https://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer AG products conducted in Europe.

http://clinicaltrials.bayer.com/

Click here to find results for studies related to Bayer Healthcare products.

Other Identifiers

15982

Identifier Type: -

Identifier Source: org_study_id

2012-003649-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id