E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038407 |
E.1.2 | Term | Renal cell cancer |
E.1.2 | System Organ Class | 100000004864 |
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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
2. 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
3. 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).
4. 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)
5. Subjects must be >18 years in age
6. 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
7. 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
8. Patients should have had surgery at least 4 weeks but no more than 3 months
(91 days) prior to treatment start date
9. Serum Amylase < 1.5 x upper limit of normal
10. Prothrombin (PT) or INR (International Normalized Ratio) and Prothrombin Time
(PTT) < 1.5 x upper limit of normal
11. WHO Performance Status 0 or 1 (Appendix 2)
12. Written Informed Consent obtained
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E.4 | Principal 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 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
6. Prior malignancy (except for cervical carcinoma in situ or adequately treated
basal cell carcinoma)
7. Metastatic disease
8. Concomitant medications which have adverse interactions with sorafenib:
rifampin, 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.5.1.1 | Timepoint(s) of evaluation of this end point |
A date is not currently set for the primary end point analysis, this will require a certain number of events to occur |
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E.5.2 | Secondary end point(s) |
The first three outcomes listed below relate to efficacy. The fourth relates to cost-effectiveness. The fifth relates to safety. The remainder are primarily of scientific interest.
1. Metastasis free survival (MFS)-the interval from randomisation to first evidence of metastases or death from RCC.
2.RCC specific survival time, i.e. the time from randomisation to dath from RCC.
3.Overall survival, i.e. the time from randomisation to death from any cause, including RCC.
4.Cost effectiveness (health economics).
5.Toxicity
6.Biological characteristics of resected primary RCC (VHL,VEGFR2,FGF2,B-RAF,MEK,ERK):Tumour samples will be examined for activation of relevant signalling pathways,and their association with outcome will be studied (TRANSORCE).
7.Genetic epidemiology:Tumour tissue and paired constitutional DNA form the tumour sample will be analysed to examine the relationship between tumour genotypes,expression, and outcome and between constitutional genotype and outcome.
8.Corroboration of Leibovich prognostic score.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
No date set for the secondary end point analysis. |
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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 | Yes |
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 | No |
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 | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
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 |