None listed
Conditions
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.
Interventions
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
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.
Sponsors
Medical Research Council
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed