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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01774344




Registration number
NCT01774344
Ethics application status
Date submitted
21/01/2013
Date registered
24/01/2013
Date last updated
20/08/2020

Titles & IDs
Public title
Study of Regorafenib After Sorafenib in Patients With Hepatocellular Carcinoma
Scientific title
A Randomized, Double Blind, Placebo Controlled, Multicenter Phase III Study of Regorafenib in Patients With Hepatocellular Carcinoma (HCC) After Sorafenib
Secondary ID [1] 0 0
2012-003649-14
Secondary ID [2] 0 0
15982
Universal Trial Number (UTN)
Trial acronym
RESORCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Regorafenib (Stivarga, BAY73-4506)
Treatment: Drugs - Placebo

Experimental: 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)

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


Treatment: Drugs: Regorafenib (Stivarga, BAY73-4506)
Regorafenib, 40 mg tablets

Treatment: Drugs: Placebo
Placebo tablets matching in appearance
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
From randomization (Day 1) of the first subject until 419 days later
Secondary outcome [1] 0 0
Time to Progression (TTP)
Timepoint [1] 0 0
From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)
Secondary outcome [2] 0 0
Progression Free Survival (PFS)
Timepoint [2] 0 0
From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks)
Secondary outcome [3] 0 0
Objective Tumor Response Rate (ORR)
Timepoint [3] 0 0
From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)
Secondary outcome [4] 0 0
Disease Control Rate (DCR)
Timepoint [4] 0 0
From date of randomization until 30 days after last study treatment (assessed every 6 weeks until PD; and after 8 cycle assessed every 12 weeks) (approximately 33 months)

Eligibility
Key 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 .
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/07/2019
Sample size
Target
Accrual to date
Final
573
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Liverpool
Recruitment hospital [3] 0 0
- Herston
Recruitment hospital [4] 0 0
- Clayton
Recruitment hospital [5] 0 0
- Box Hill
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment outside Australia
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United States of America
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California
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Colorado
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District of Columbia
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Illinois
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Pennsylvania
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Virginia
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Washington
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Argentina
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Buenos Aires
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Austria
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Oberösterreich
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Austria
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Steiermark
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Austria
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Wien
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Belgium
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Bruxelles - Brussel
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Belgium
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La Louviere
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Brazil
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Bahia
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Brazil
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Sao Paulo
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China
State/province [22] 0 0
Anhui
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China
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Fujian
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China
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Guangdong
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China
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Guangxi
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China
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Heilongjiang
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China
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Hubei
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China
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Hunan
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China
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Jiangsu
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China
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Liaoning
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China
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Shaanxi
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China
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Sichuan
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China
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Beijing
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China
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Chongqing
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China
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Shanghai
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China
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Tianjin
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Czechia
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Hradec Kralove
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Czechia
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Olomouc
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Czechia
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Praha 2
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France
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Angers
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France
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Caen
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Clichy
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Creteil
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Dijon
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Lille
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Lyon
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Marseille
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Montpellier Cedex
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Nice Cedex 3
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France
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Paris
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France
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Perpignan
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Reims Cedex
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France
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Rennes Cedex
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France
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Toulouse
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France
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Vandoeuvre les Nancy
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Villejuif Cedex
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Germany
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Baden-Württemberg
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Germany
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Bayern
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Germany
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Hessen
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Germany
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Niedersachsen
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Germany
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Nordrhein-Westfalen
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Germany
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Rheinland-Pfalz
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Germany
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Sachsen-Anhalt
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Germany
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Berlin
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Germany
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Hamburg
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Kaposvar
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Campania
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Lazio
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Italy
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Liguria
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Italy
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Piemonte
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Puglia
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Sardegna
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Toscana
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Chiba
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Fukuoka
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Kumamoto
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Japan
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Tochigi
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Japan
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Tokyo
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Korea, Republic of
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Busan Gwang''yeogsi
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Korea, Republic of
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Daegu
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Netherlands
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Leiden
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Russian Federation
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Barnaul
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Russian Federation
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Moscow
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Singapore
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Singapore
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Spain
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Asturias
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Alicante
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Barcelona
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Córdoba
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Spain
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Madrid
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Spain
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Zaragoza
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Switzerland
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Ticino
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Switzerland
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Bern
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Taiwan
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Kaohsiung
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
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West Midlands
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United Kingdom
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West Yorkshire
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United Kingdom
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Bristol
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01774344
Trial related presentations / publications
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.
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. Erratum In: Lancet. 2017 Jan 7;389(10064):36. doi: 10.1016/S0140-6736(16)32615-0.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01774344