E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038407 |
E.1.2 | Term | Renal cell cancer |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The standard treatment for patients with a kidney cancer which has not spread to other organs is to remove all or part of the diseased kidney (nephrectomy). The standard policy after this is watchful waiting. This means no treatment, but having regular checks so that if the cancer does come back it is caught early.
The principal research question is whether sorafenib increases disease free survival (DFS) i.e reduces the risk of kidney cancer returning.
SORCE aims to answer two questions. The first question is whether at least one year of treatment with sorafenib increases DFS compared with placebo. The second question is about the duration of sorafenib, and whether an additional 2 years of sorafenib (as given in Arm C) increases DFS compared to placebo. |
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E.2.2 | Secondary objectives of the trial |
The secondary research objectives are to assess renal cell carcinoma specific survival time, overall survival, cost effectiveness, toxicity, assessment of biological characteristics of the removed kidney tumour, and corroboration of Leibovich Prognostic score.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologically proven RCC (all celltypes 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 2. Patients with a pulonary nodule may be eligle but the nodule needs to be <5 mm diameter and have been stable for at least 3 months 3. Patients with "Intermediate" or "High" risk per the Leibovich score 3 to 11 4.Subjects must be >18 years in age without any other medical condition expected to reduce their life expectancy below 10 years from the time of study entry 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 breast feed are not eligible for the study 6. 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 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 INR (International Normalized Ratio) and Prothrombin Time (PTT) < 1.5 x upper limit of normal 10.WHO Performance Status 0 or 1 11. Written Informed Consent obtained
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E.4 | Principal exclusion criteria |
1.Prior anti-cancer treatment other than nephrectomy 2.Suspected allergy to sorafenib 3.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 4.Active clinically serious bacterial or fungal infections 5.Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C 6.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 7.Prior malignancy (except for cervical carcinoma in situ or adequately treated basal cell carcinoma) 8.Concomitant medications which have adverse interactions with sorafenib: rifampin, grapefruit juice, ritonavir, ketoconazole, itraconazole and St John's Wort. 9.Patients with uncontrolled hypertension
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E.5 End points |
E.5.1 | Primary end point(s) |
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). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial will be considered closed for regulatory purposes after the last patient entered has completed their protocol treatment. Further observational follow-up of all patients enrolled in the trial may continue indefinitely. This will initially be via hospitals and clinics, but in the longer term may exploit national registers |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |