The revised aims of the SORCE trial are:1. Does up to three years of treatment with sorafenib increase DFS compared with placebo: a comparison of Arm C vs Arm A2. If the answer to question (i) is yes, does one year of sorafenib (Arm B) increase DFS…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is disease free survival (DFS) (i.e. time from
randomisation to first evidence of local recurrence or distant metastases or
death
from RCC).
Secondary outcome
The secondary outcome measures include RCC-specific survival time (i.e.
time to death from RCC), overall survival (OS), cost effectiveness, toxicity,
biological
characteristics of resected primary RCC (VHL, VEGFR2, FGF2, B-RAF, MEK, ERK) and
corroboration of Leibovich Prognostic Score.
Background summary
Annually, 208,000 new cases and 102,000 deaths result each year from renal cell
carcinoma (RCC) throughout the world.
At present in primary RCC the only treatment that is routinely used is total or
partial nephrectomy.
Methylation or inactivating mutations of the Von Hippel Lindau (VHL) gene are
present in around 70% of clear cell carcinomas, the commonest form of RCC.
Inactivation of the VHL gene results in up regulation of vascular endothelial
growth
factor (VEGF) and platelet derived growth factor (PDGF).
VEGF and PDGF act on cell receptors (VEGFR and PDGFR) to stimulate the formation
and stabilisation of new blood vessels which are crucial for the growth of
tumours2.
Recently, the oral kinase inhibitor sorafenib (known as Nexavar) has become
available. Sorafenib inhibits several kinases known to be important in the
pathobiology of RCC including C-RAF, B-RAF, VEGFR2, VEGFR3 and PDGFR3.
Previous studies with patients with renal-cell carcinoma that was resistant to
standard therapy were
randomised to receive either continuous treatment with oral Sorafenib (at a
dose of
400 mg twice daily) or placebo, showed a statistically significant benefit of
Sorafenib over placebo.
In view of the promising results of sorafenib when used in the advanced disease
setting, a trial in the adjuvant setting is both timely and worthwhile.
Study objective
The revised aims of the SORCE trial are:
1. Does up to three years of treatment with sorafenib increase DFS compared
with placebo: a comparison of Arm C vs Arm A
2. If the answer to question (i) is yes, does one year of sorafenib (Arm B)
increase DFS compared to placebo (Arm A)?
See protocol section 12.4 for more information on the revised analysis plan.
Study design
SORCE is a multi-centre randomised phase III double-blind placebo-controlled
study
Intervention
Patients will be randomly assigned to 3 years of placebo (Arm A), 1 year
sorafenib
followed by 2 years placebo (Arm B) or 3 years sorafenib (Arm C). Sorafenib
will be
given at 400 mg po (per oral) bd doses.
Patients with disease progression who progress on Arms 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.
Study burden and risks
see page 40 of the protocol and pages 4/5 of the Patient Information sheet
Geert Grooteplein zuid 10
GA Nijmegen 6525
NL
Geert Grooteplein zuid 10
GA Nijmegen 6525
NL
Listed location countries
Age
Inclusion criteria
-Histologically proven RCC(All cell types of RCC are eligible, except pure
oncocytoma as distinct from an RCC with oncocytic features).
-No evidence of residual macroscopic disease on post-operative CT scan after
resection of RCC. Patients with clear cell or non-clear cell tumours are
eligible
-Patients with a pulmonary nodule may be eligible but the nodule needs to be
<5mm diameter and have been stable for at least 3 months (confirmed by CT
scan).
-Patients with *Intermediate* or *High* risk per the Leibovich score 3 to 11
(Special pathology guidelines for Leibovich scoring of tumour samples see
appendix 1)
-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 the study and for 9
months afterwards. Women who wish to breast feed are not eligible for the
study
-Adequate bone marrow function (WBC > 3.4x109/l, platelets > 99x109/l), renal
function (creatinine < 2.5 x upper limit of normal and hepatic function (LFT <
1.5 x upper limit of normal) within 14 days prior to randomisation
- Patients should have had surgery at least 4 weeks but no more than 3 months
(91 days) prior to treatment start date
- Serum Amylase < 1.5 x upper limit of normal
-Prothrombin (PT) or INR (International Normalized Ratio) and Prothrombin Time
(PTT) < 1.5 x upper limit of normal
-WHO Performance Status 0 or 1 (Appendix 2)
-Written Informed Consent obtained
Exclusion criteria
-Prior anti-cancer treatment for RCC 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 > 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. 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
-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
-Patients with a pulmonary nodule *5 mm diameter or multiple
pulmonary nodules.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-006079-19-NL |
| ISRCTN | ISRCTN38934710 |
| CCMO | NL24110.091.08 |