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Trial registered on ANZCTR


Registration number
ACTRN12609000048280
Ethics application status
Approved
Date submitted
7/11/2008
Date registered
21/01/2009
Date last updated
24/02/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
A phase III study comparing Sorafenib with placebo in patients who have had kidney cancer removed (SORCE)
Scientific title
A phase III randomised double-blind study comparing Sorafenib with placebo in patients with resected primary renal cell carcinoma at high or intermediate risk of relapse.
Secondary ID [1] 282450 0
NCT00492258
Secondary ID [2] 282451 0
ISRCTN38934710
Universal Trial Number (UTN)
Trial acronym
SORCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal cancer 3948 0
Condition category
Condition code
Cancer 4143 4143 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention group 1 and group 2 will self administer 400 mg of sorafenib (2 x 200 mg tablets) and Intervention group 3 will self-administer matching placebo tablets once per day for 21 days. At 21 days the dose will be increased to 400 mg (2 x 200mg tablets) or matching placebo twice per day if the patient has not experienced greater than Grade I skin toxicity or greater than Grade II of any other toxicity. Dose escalation may be deferred until at least the planned 6 week visit if toxicities do occur. After the first 21 days Intervention group 1 and group 2 will receive sorafenib at 400mg oral dose (2 x 200mg tablets) twice daily until the end of the first year, followed by Placebo (2 x oral sugar pills twice daily for 2 years). Intervention group 2 will receive sorafenib at 400mg oral dose (2 x 200mg tablets) twice daily until the completion of the three years. The tablets should be swallowed whole with a glass of water. The tablets should be taken without food (at least 1 hour before or 2 hours after eating) or with a moderate fat meal. Twice daily doses should be separated by approximately 12 hours.
Intervention code [1] 3742 0
Treatment: Drugs
Comparator / control treatment
The comparator/control gorup will receive placebo (2 x oral sugar pills twice daily for 3 years).
Control group
Placebo

Outcomes
Primary outcome [1] 5042 0
Disease-free survival, measured by 6-monthly computer tomography (CT) of chest, abomen and pelvis, with 6-monthly chest x-rays in-between.
Timepoint [1] 5042 0
Baseline, 3 weeks, 6 weeks and 3 months post-randomisation, then 3-monthly until 3 years post-randomisation. 6-monthly chest x-rays only between 3 and 6 years post-randomisation. Yearly chest x-rays only following first 5 years.
Secondary outcome [1] 8708 0
Renal cell carcinoma (RCC)-specific survival time
Timepoint [1] 8708 0
Baseline, 3 weeks, 6 weeks and 3 months post-randomisation, then 3-monthly until 5 years post-randomisation. Yearly following first 5 years.
Secondary outcome [2] 8709 0
overall survival
Timepoint [2] 8709 0
Clinical examination follow-up of patients at 3 weeks, 6 weeks and 3 months post-randomisation, then 3-monthly until 3 years post-randomisation. 6-monthly between 3 and 6 years post-randomisation. Yearly following first 5 years.
Secondary outcome [3] 8711 0
Toxicities will be measured using Cancer Toxicity Criteria for Adverse Events (CTCAE) version 3.0.
Timepoint [3] 8711 0
Baseline, 3 weeks, 6 weeks and 3 months post-randomisation, then 3-monthly until 5 years post-randomisation. Yearly following first 5 years.
Secondary outcome [4] 8712 0
biological characteristics of resected primary RCC (ie the Von Hippel Lindau (VHL) gene, the vascular endothelial growth factor receptor 2 (VEGFR2) gene, fibroblast growth factor 2 (FGF2), B-RAF, MEK, ERK).
Timepoint [4] 8712 0
Measured from tissue collected at time of surgery and blood collected at time of randomisation.
Secondary outcome [5] 8713 0
Leibovich Calculated Score for risk of relapse in renal cell carcinoma
Timepoint [5] 8713 0
At time of surgery.

Eligibility
Key inclusion criteria
Inclusion criteria: Histologically proven renal cell carcinoma. No evidence of residual macroscopic disease on post-operative Computerised Tomography (CT) scan after resection of renal cell carcinoma. Patients with clear cell or non-clear cell tumours are eligible. Patients with "intermediate" or "high" risk per the Leibovich score 3 to 11. Subjects must be >18 years in age. Women of childbearing age must have a negative pregnancy test and must use adequate contraception during the treatment phase of hte study and for 9 months afterwards. Women who wish to breast feed are not eligible for the study. Adequate bone marrow function (White Blood Cell (WBC) > 3.4 x 109/L, platelets > 99 x 109/L) renal function (creatinine < 2.5 x the Upper Limit of Normal (ULN)) and hepatic function (Liver Function Test (LFT) < 1.5 x ULN) within 14 days prior to randomisation. Patients should have had surgery at least 4 weeks but no more than 3 months (91d) prior to treatment start date. Serum amylase < 1.5 x ULN Prothrombin or International Normalised Ratio (INR) and prothrombin time < 1.5 x ULN World Health Organisation (WHO) performance status 0 or 1. Written informed consent obtained.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior anti-cancer treatment for renal cell carcinoma other than nephrectomy Cardiac arrhythmias requiring anti-arrhythmics (beta blockers and digoxin are allowed), symptomatic coronary artery disease or ischaemia, myocardial infarction within the last 6 months, congestive cardiac failure > (New York Heart Association (NYHA) class II. Active clinically serious bacterial or fungal infections. Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C. Pregnant or breast-feeding patients. Prior malignancy (except for cervical carcinoma in situ or adequately treated basal cell carcinoma). Concomitant medications which have adverse interactions with sorafenib: rifampin, grapefruit juice, ritonavir, ketoconazole, itraconazole and St John's Wort. Patients with uncontrolled hypertension.

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?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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,VIC,ACT,QLD,SA,WA,TAS
Recruitment outside Australia
Country [1] 1360 0
Netherlands
State/province [1] 1360 0
Country [2] 1361 0
United Kingdom
State/province [2] 1361 0
Country [3] 1362 0
Denmark
State/province [3] 1362 0
Country [4] 1363 0
Spain
State/province [4] 1363 0
Country [5] 1364 0
Belgium
State/province [5] 1364 0
Country [6] 1365 0
France
State/province [6] 1365 0

Funding & Sponsors
Funding source category [1] 4132 0
Government body
Name [1] 4132 0
Clinical Trials Advisory and Awards Committee (CTAAC): Cancer Research UK
Address [1] 4132 0
Cancer Research UK
61 Lincoln's Inn Fields
London
WC2A 3PX
Country [1] 4132 0
United Kingdom
Funding source category [2] 4261 0
Commercial sector/Industry
Name [2] 4261 0
Bayer AG
Address [2] 4261 0
Bayer AG
51368 Leverkusen
Country [2] 4261 0
Germany
Funding source category [3] 269998 0
Other Collaborative groups
Name [3] 269998 0
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Address [3] 269998 0
Lifehouse, Level 6, 119-143 Missenden Road, Camperdown NSW 2050
Country [3] 269998 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Medical Research Council
Address
222 Euston Road
London
NW1 2DA
Country
United Kingdom
Secondary sponsor category [1] 3717 0
University
Name [1] 3717 0
University of Sydney
Address [1] 3717 0
NHMRC Clinical Trials Centre
Level 6, Medical Foundations Building, 92-94 Parramatta Road Camperdown NSW 2050
Country [1] 3717 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271958 0
Sydney Local Health District Ethics Review Committee (RPAH zone)
Ethics committee address [1] 271958 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Road
CAMPERDOWN NSW 2050
Ethics committee country [1] 271958 0
Australia
Date submitted for ethics approval [1] 271958 0
Approval date [1] 271958 0
05/11/2008
Ethics approval number [1] 271958 0
AU RED Reference Number: 08/CIC/26
Cancer Institute NSW Reference Number: 2008C/08/060
Ethics committee name [2] 294475 0
ACT Health Human Research Ethics Committee
Ethics committee address [2] 294475 0
Building 10
Level 6
Canberra Hospital
Garran ACT 2605
Ethics committee country [2] 294475 0
Australia
Date submitted for ethics approval [2] 294475 0
Approval date [2] 294475 0
11/05/2009
Ethics approval number [2] 294475 0
Ethics committee name [3] 294476 0
The Alfred Hospital Ethics Committee
Ethics committee address [3] 294476 0
OFFICE OF ETHICS & RESEARCH GOVERNANCE
Ground Floor
Linay Pavilion
The Alfred
Prahran VIC 3181
Ethics committee country [3] 294476 0
Australia
Date submitted for ethics approval [3] 294476 0
Approval date [3] 294476 0
21/05/2009
Ethics approval number [3] 294476 0
Ethics committee name [4] 294477 0
Eastern Health Human Research Ehics Committee
Ethics committee address [4] 294477 0
Level 2
5 Arnold Street
Box Hill VIC 3128
Ethics committee country [4] 294477 0
Australia
Date submitted for ethics approval [4] 294477 0
Approval date [4] 294477 0
01/07/2010
Ethics approval number [4] 294477 0
Ethics committee name [5] 294478 0
Austin Health Human Research Ethics Committee
Ethics committee address [5] 294478 0
145 Studley Road
Heidelberg
VIC 3084
Ethics committee country [5] 294478 0
Australia
Date submitted for ethics approval [5] 294478 0
Approval date [5] 294478 0
17/10/2007
Ethics approval number [5] 294478 0
Ethics committee name [6] 294479 0
Bellberry Limited Human Research Ethics Committee
Ethics committee address [6] 294479 0
129 Glen Osmond Road
Eastwood
SA 5063
Ethics committee country [6] 294479 0
Australia
Date submitted for ethics approval [6] 294479 0
Approval date [6] 294479 0
30/11/2010
Ethics approval number [6] 294479 0
Ethics committee name [7] 294480 0
The Royal Brisbane & Women’s Hospital Human Research Ethics Committee
Ethics committee address [7] 294480 0
Level 7, Block 7
Royal Brisbane and Women's Hospital
Metro North Health Service District
Herston
QLD 4006
Ethics committee country [7] 294480 0
Australia
Date submitted for ethics approval [7] 294480 0
Approval date [7] 294480 0
29/06/2009
Ethics approval number [7] 294480 0
Ethics committee name [8] 294481 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [8] 294481 0
Level 3
Hanson Institute
Adelaide SA 5000
Ethics committee country [8] 294481 0
Date submitted for ethics approval [8] 294481 0
Approval date [8] 294481 0
05/10/2007
Ethics approval number [8] 294481 0
Ethics committee name [9] 294482 0
The Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [9] 294482 0
Flinders Medical Centre
Bedford Park
SA 5042
Ethics committee country [9] 294482 0
Australia
Date submitted for ethics approval [9] 294482 0
Approval date [9] 294482 0
05/11/2009
Ethics approval number [9] 294482 0
Ethics committee name [10] 294483 0
Sir Charles Giardner Group Human Research Ethics Committee
Ethics committee address [10] 294483 0
Level 2 A Block
Hospital Ave
Nedlands
WA 6009
Ethics committee country [10] 294483 0
Australia
Date submitted for ethics approval [10] 294483 0
Approval date [10] 294483 0
14/07/2009
Ethics approval number [10] 294483 0
Ethics committee name [11] 294484 0
South Metropolitam Area Health Service Human Research Ethics Committee
Ethics committee address [11] 294484 0
Level 2, Southern Research Facility (Perkins Building)
Fiona Stanley Hospital
11 Robin Warren Drive
MURDOCH WA 6150
Ethics committee country [11] 294484 0
Australia
Date submitted for ethics approval [11] 294484 0
Approval date [11] 294484 0
03/06/2009
Ethics approval number [11] 294484 0
Ethics committee name [12] 294485 0
Human Research Ethics Committee of Tasmania
Ethics committee address [12] 294485 0
Office of Research Services, University of Tasmania, Private Bag 1, Hobart, TAS, 7001
Ethics committee country [12] 294485 0
Australia
Date submitted for ethics approval [12] 294485 0
Approval date [12] 294485 0
13/08/2009
Ethics approval number [12] 294485 0

Summary
Brief summary
This study looks at the effectiveness the drug Sorafenib on treating patients who have had kidney cancer removed surgically.


Who is it for?
You can join this study if you have had primary renal cell carcinoma and this has been removed by surgery, and you are at high or intermediate risk of relapse.


Trial details
Participants will be randomly divided into three groups. Group 1 will receive a non-active substance (placebo) for 3 years. Group 2 will receive Sorafenib for 1 year followed by placebo for 2 years. Group 3 will receive Sorafenib only for 3 years. Treatment is by tablets taken twice a day.

At the moment there are no treatments that have been proven to reduce the risk of kidney cancer returning after it has been removed by an operation. Sorafenib is a drug that acts starving cancers of their blood supply and will often shrink or stop cancer growing for prolonged periods of time. The study aims to see whether Sorafineb reduces the risk of kidney cancer returning and whether it increases survival rate.
Trial website
www.anzup.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29107 0
Prof Ian Davis
Address 29107 0
Eastern Health Clinical School
Faculty of Medicine, Nursing and Health Sciences
Level 2, 5 Arnold St
Box Hill
Vic 3128
Australia
Country 29107 0
Australia
Phone 29107 0
+61 2 9562 5000
Fax 29107 0
Email 29107 0
sorce@ctc.usyd.edu.au
Contact person for public queries
Name 12264 0
Ms SORCE Trial Coordinator
Address 12264 0
NHMRC Clinical Trials Centre
The Lifehouse Building
Level 6
119 -143 Missenden Road
Camperdown NSW 2050
Country 12264 0
Australia
Phone 12264 0
(02) 9562 5000
Fax 12264 0
(02) 9562 5094
Email 12264 0
sorce@ctc.usyd.edu.au
Contact person for scientific queries
Name 3192 0
Ms SORCE Trial Coordinator
Address 3192 0
NHMRC Clinical Trials Centre
The Lifehouse Building
Level 6
119 -143 Missenden Road
Camperdown NSW 2050
Country 3192 0
Australia
Phone 3192 0
(02) 9562 5000
Fax 3192 0
(02) 9562 5094
Email 3192 0
sorce@ctc.usyd.edu.au

No data has been provided for results reporting
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary