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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

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Argentina
State/province [14] 0 0
Buenos Aires
Country [15] 0 0
Austria
State/province [15] 0 0
Oberösterreich
Country [16] 0 0
Austria
State/province [16] 0 0
Steiermark
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Bruxelles - Brussel
Country [19] 0 0
Belgium
State/province [19] 0 0
La Louviere
Country [20] 0 0
Brazil
State/province [20] 0 0
Bahia
Country [21] 0 0
Brazil
State/province [21] 0 0
Sao Paulo
Country [22] 0 0
China
State/province [22] 0 0
Anhui
Country [23] 0 0
China
State/province [23] 0 0
Fujian
Country [24] 0 0
China
State/province [24] 0 0
Guangdong
Country [25] 0 0
China
State/province [25] 0 0
Guangxi
Country [26] 0 0
China
State/province [26] 0 0
Heilongjiang
Country [27] 0 0
China
State/province [27] 0 0
Hubei
Country [28] 0 0
China
State/province [28] 0 0
Hunan
Country [29] 0 0
China
State/province [29] 0 0
Jiangsu
Country [30] 0 0
China
State/province [30] 0 0
Liaoning
Country [31] 0 0
China
State/province [31] 0 0
Shaanxi
Country [32] 0 0
China
State/province [32] 0 0
Sichuan
Country [33] 0 0
China
State/province [33] 0 0
Beijing
Country [34] 0 0
China
State/province [34] 0 0
Chongqing
Country [35] 0 0
China
State/province [35] 0 0
Shanghai
Country [36] 0 0
China
State/province [36] 0 0
Tianjin
Country [37] 0 0
Czechia
State/province [37] 0 0
Hradec Kralove
Country [38] 0 0
Czechia
State/province [38] 0 0
Olomouc
Country [39] 0 0
Czechia
State/province [39] 0 0
Praha 2
Country [40] 0 0
France
State/province [40] 0 0
Angers
Country [41] 0 0
France
State/province [41] 0 0
Caen
Country [42] 0 0
France
State/province [42] 0 0
Clichy
Country [43] 0 0
France
State/province [43] 0 0
Creteil
Country [44] 0 0
France
State/province [44] 0 0
Dijon
Country [45] 0 0
France
State/province [45] 0 0
La Tronche
Country [46] 0 0
France
State/province [46] 0 0
Lille
Country [47] 0 0
France
State/province [47] 0 0
Lyon
Country [48] 0 0
France
State/province [48] 0 0
Marseille
Country [49] 0 0
France
State/province [49] 0 0
Montpellier Cedex
Country [50] 0 0
France
State/province [50] 0 0
Nice Cedex 3
Country [51] 0 0
France
State/province [51] 0 0
Paris
Country [52] 0 0
France
State/province [52] 0 0
Perpignan
Country [53] 0 0
France
State/province [53] 0 0
Reims Cedex
Country [54] 0 0
France
State/province [54] 0 0
Rennes Cedex
Country [55] 0 0
France
State/province [55] 0 0
Toulouse
Country [56] 0 0
France
State/province [56] 0 0
Vandoeuvre les Nancy
Country [57] 0 0
France
State/province [57] 0 0
Villejuif Cedex
Country [58] 0 0
Germany
State/province [58] 0 0
Baden-Württemberg
Country [59] 0 0
Germany
State/province [59] 0 0
Bayern
Country [60] 0 0
Germany
State/province [60] 0 0
Hessen
Country [61] 0 0
Germany
State/province [61] 0 0
Niedersachsen
Country [62] 0 0
Germany
State/province [62] 0 0
Nordrhein-Westfalen
Country [63] 0 0
Germany
State/province [63] 0 0
Rheinland-Pfalz
Country [64] 0 0
Germany
State/province [64] 0 0
Sachsen-Anhalt
Country [65] 0 0
Germany
State/province [65] 0 0
Berlin
Country [66] 0 0
Germany
State/province [66] 0 0
Hamburg
Country [67] 0 0
Hungary
State/province [67] 0 0
Budapest
Country [68] 0 0
Hungary
State/province [68] 0 0
Debrecen
Country [69] 0 0
Hungary
State/province [69] 0 0
Kaposvar
Country [70] 0 0
Italy
State/province [70] 0 0
Campania
Country [71] 0 0
Italy
State/province [71] 0 0
Emilia-Romagna
Country [72] 0 0
Italy
State/province [72] 0 0
Lazio
Country [73] 0 0
Italy
State/province [73] 0 0
Liguria
Country [74] 0 0
Italy
State/province [74] 0 0
Lombardia
Country [75] 0 0
Italy
State/province [75] 0 0
Piemonte
Country [76] 0 0
Italy
State/province [76] 0 0
Puglia
Country [77] 0 0
Italy
State/province [77] 0 0
Sardegna
Country [78] 0 0
Italy
State/province [78] 0 0
Toscana
Country [79] 0 0
Italy
State/province [79] 0 0
Veneto
Country [80] 0 0
Japan
State/province [80] 0 0
Chiba
Country [81] 0 0
Japan
State/province [81] 0 0
Fukuoka
Country [82] 0 0
Japan
State/province [82] 0 0
Kanagawa
Country [83] 0 0
Japan
State/province [83] 0 0
Kumamoto
Country [84] 0 0
Japan
State/province [84] 0 0
Osaka
Country [85] 0 0
Japan
State/province [85] 0 0
Tochigi
Country [86] 0 0
Japan
State/province [86] 0 0
Tokyo
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Busan Gwang''yeogsi
Country [88] 0 0
Korea, Republic of
State/province [88] 0 0
Daegu
Country [89] 0 0
Korea, Republic of
State/province [89] 0 0
Seoul
Country [90] 0 0
Netherlands
State/province [90] 0 0
Amsterdam
Country [91] 0 0
Netherlands
State/province [91] 0 0
Leiden
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Barnaul
Country [93] 0 0
Russian Federation
State/province [93] 0 0
Moscow
Country [94] 0 0
Singapore
State/province [94] 0 0
Singapore
Country [95] 0 0
Spain
State/province [95] 0 0
Asturias
Country [96] 0 0
Spain
State/province [96] 0 0
Alicante
Country [97] 0 0
Spain
State/province [97] 0 0
Barcelona
Country [98] 0 0
Spain
State/province [98] 0 0
Córdoba
Country [99] 0 0
Spain
State/province [99] 0 0
Madrid
Country [100] 0 0
Spain
State/province [100] 0 0
Zaragoza
Country [101] 0 0
Switzerland
State/province [101] 0 0
Ticino
Country [102] 0 0
Switzerland
State/province [102] 0 0
Bern
Country [103] 0 0
Taiwan
State/province [103] 0 0
Kaohsiung
Country [104] 0 0
Taiwan
State/province [104] 0 0
Taipei
Country [105] 0 0
Taiwan
State/province [105] 0 0
Taoyuan
Country [106] 0 0
United Kingdom
State/province [106] 0 0
West Midlands
Country [107] 0 0
United Kingdom
State/province [107] 0 0
West Yorkshire
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Bristol
Country [109] 0 0
United Kingdom
State/province [109] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents