SORCE: 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

ISRCTN	ISRCTN38934710
DOI	https://doi.org/10.1186/ISRCTN38934710
EudraCT/CTIS number	2006-006079-19
ClinicalTrials.gov number	NCT00492258
Secondary identifying numbers	ACTRN12609000048280; RE05

Submission date: 31/05/2007
Registration date: 30/08/2007
Last edited: 08/04/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-sorafenib-or-placebo-after-surgery-for-kidney-cancer-that-has-not-spread

Contact information

Prof Tim Eisen
Scientific

Oncology Centre
Box 193
Addenbrooke's Hospital
Robinsons Way
Cambridge
CB2 2RE
United Kingdom

Email	tgqe2@cam.ac.uk

Study information

Study design	Randomised double-blind placebo-controlled multi-centre study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	SORCE: 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
Study acronym	SORCE
Study hypothesis	SORCE aims to answer two questions: 1. Whether at least one year of treatment with sorafenib increases Disease-Free Survival (DFS) compared with placebo. 2. Whether three years of treatment with sorafenib increases DFS compared to one year of treatment.
Ethics approval(s)	South East Research Ethics Committee, South East Coast Health Authority, 02/04/2007, ref: 07/MRE01/10
Condition	Primary renal cell carcinoma
Intervention	Patients will be randomly assigned to one of the following: Arm A: 3 years of placebo Arm B: 1 year of sorafenib followed by 2 years of placebo Arm C: 3 years of sorafenib Sorafenib will be given at 400 mg po (per oral) bd (twice daily) doses. Patients with disease progression who are in Arm A or B within 3 years of start of treatment whilst on placebo will be offered compassionate use of sorafenib at the standard dose of 400 mg po bd until further progression/toxicity. This is referred to throughout the protocol as open-label sorafenib.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Sorafenib
Primary outcome measure	Disease Free Survival (DFS) (i.e. time from randomisation to first evidence of local recurrence or distant metastases or death from RCC)
Secondary outcome measures	1. RCC-specific survival time (i.e. time to death from RCC) 2. Overall Survival (OS) 3. Cost effectiveness 4. Toxicity 5. Biological characteristics of resected primary RCC: 5.1. von Hippel Lindau (VHL) protein 5.2. Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) 5.3. Fibroblast Growth Factor 2 (FGF2) 5.4. B-Raf 5.5. MAPK ERK kinase (MEK) 5.6. Extracellular signal-Regulated Kinase (ERK) 6. Corroboration of Leibovich Prognostic Score (9 years after first patient entry)
Overall study start date	01/06/2007
Overall study end date	01/06/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	1656
Total final enrolment	1711
Participant inclusion criteria	1. Histologically proven Renal Cell Carcinoma (RCC) 2. No evidence of residual macroscopic disease on post-operative Computed Tomography (CT) scan after resection of RCC. Patients with clear cell or non-clear cell tumours are eligible 3. Patients with 'Intermediate' or 'High' risk per the Leibovich score 3 to 11 4. Subjects must be >18 years of age 5. Women of childbearing age must have a negative pregnancy test and must use adequate contraception during the treatment phase of the study and for 9 months afterwards. Women who wish to breastfeed are not eligible for the study 6. Adequate bone marrow function (White Blood Cells > 3.4x109/l, platelets > 99x109/l), renal function (creatinine < 2.5 x upper limit of normal and hepatic function (liver function test [LFT] < 1.5 x upper limit of normal) within 14 days prior to randomisation 7. Patients should have had surgery at least 4 weeks but no more than 3 months prior to treatment start date 8. Serum amylase < 1.5 x upper limit of normal 9. ProThrombin (PT) or International Normalized Ratio (INR) and ProThrombin Time (PTT) < 1.5 x upper limit of normal 10. World Health Organization Performance Status 0 or 1 11. Written Informed Consent obtained
Participant exclusion criteria	1. Prior anti-cancer treatment for RCC other than nephrectomy 2. 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 > NYHA Class II 3. Active clinically serious bacterial or fungal infections 4. Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C 5. Pregnant or breastfeeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate birth control 6. Prior malignancy (except for cervical carcinoma in situ or adequately treated basal cell carcinoma) 7. Concomitant medications which have adverse interactions with sorafenib: rifampin, grapefruit juice, ritonavir, ketoconazole, itraconazole and St John's Wort 8. Patients with uncontrolled hypertension
Recruitment start date	01/06/2007
Recruitment end date	01/06/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Addenbrooke's Hospital

Cambridge
CB2 2RE
United Kingdom

Sponsor information

Medical Research Council (UK)
Government

MRC Centre London
Second Floor
Stephenson House
158-160 North Gower Street
London
NW1 2ND
United Kingdom

Email	iv@centre-london.mrc.ac.uk
Website	http://www.ctu.mrc.ac.uk
"ROR"	https://ror.org/03x94j517

Funders

Funder type

Government

Medical Research Council (UK)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Cancer Research UK, Clinical Trials Advisory and Awards Committee (CTAAC)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Bayer (educational grant plus free Sorafenib/matched placebo for all patients) (International)
Government organisation / For-profit companies (industry)

Alternative name(s): Bayer AG, Bayer Corporation, Friedr. Bayer et. comp.
Location: Germany

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Lawrence NJ, Martin A, Davis ID, Troon S, Sengupta S, Hovey EJ, et al. Predicted benefits of adjuvant sorafenib after nephrectomy for renal cell carcinoma (RCC) in SORCE: an international, placebo-controlled, randomised phase 3 trial. ESMO-2017 2017; abstr. 881P. Available from: URL: http://www.esmo.org/Conferences/ESMO-2017-Congress
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	11/12/2012		Yes	No
Abstract results	baseline information	01/02/2014		No	No
Results article	results	01/02/2018		Yes	No
Results article		01/12/2020	08/04/2021	Yes	No

Editorial Notes

08/04/2021: Publication reference and total final enrolment added.
16/12/2020: Cancer Research UK lay results summary link added to Results (plain English).
11/03/2019: Publication references added.
11/10/2017: No publications found, verifying study status with principal investigator.