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Background SORCE is a randomised, double-blind trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) at intermediate or high risk of recurrence (Leibovich classification). Methods We recruited patients from 147 sites in the UK, Australia, France, Belgium, Denmark, The Netherlands and Spain and randomised them (2:3:3) between three years of placebo (A), one year of sorafenib followed by two years of placebo (B) and three years of sorafenib (C). The initial sorafenib dose was 400mg twice per day orally, amended during trial recruitment to a reduced starting dose of 400mg daily. The primary outcome is investigator-reported disease-free survival (DFS). Given the results of the ASSURE and S-TRAC trials, and blinded to SORCE outcomes, we revised the primary analysis to compare three years of sorafenib (arm C) vs placebo (arm A) to focus on the question of longer exposure to sorafenib. Results Between July 2007 and April 2013, we randomised 1711 patients; 430, 642, and 639 to arms A, B, and C respectively. Median age was 58 years; 71% male, 84% clear cell histology, 53% at intermediate risk of recurrence and 47% at high risk of recurrence. We observed no differences in DFS or OS in any of our pre-planned and pre-powered analyses: all randomised patients, high-risk patients only, and patients with clear cell RCC only. Median DFS was not reached for three years sorafenib or for placebo (HR 1.01, 95% CI 0.83 -1.23, p=0.95). We observed non-proportional hazards: restricted mean survival time (RMST) was 6.81 years for three years of sorafenib and 6.82 years for placebo, RMST difference 0.01, 95% CI -0.49 – 0.48, p=0.99. Despite offering treatment adaptations, over half of patients stopped treatment early. Grade 3 hand-foot syndrome was reported in 24% of patients on sorafenib. Conclusions Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence following nephrectomy; it is the appropriate control of our current international adjuvant RCC trial, RAMPART. Clinical trial identification ISRCTN38934710; EudraCT: 2006-006079-19; NCT00492258. Legal entity responsible for the study University College London (UCL). Funding Cancer Research UK, UK Medical Research Council, Educational Grants and Drug Supply from Bayer, Cancer Australia Support for Cancer Clinical Trials Program and University College London. Disclosure T.Q.G. Eisen: Honoraria (self), Research grant / Funding (self): Bayer; Honoraria (self), Research grant / Funding (self): Pfizer; Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Honoraria (self): Novartis; Honoraria (self): GSK; Honoraria (self): AVEO; Honoraria (self): Astellas; Honoraria (self): Boehringer Ingelheim. I.D. Davis: Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche / Genentech; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bristol-Myers Squibb. M.R. Stockler: Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Binomics; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Tilray. J.M.G. Larkin: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Achilles Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Covance; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Pharmacyclics; Research grant / Funding (institution): Aveo; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy: Eisai; Advisory / Consultancy: EUSA Pharma; Advisory / Consultancy: GSK; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Imugene; Advisory / Consultancy: Incyte; Advisory / Consultancy: iOnctura. A. Bex: Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy, Non-remunerated activity/ies: BMS; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eusa; Non-remunerated activity/ies: Roche. S. Joniau: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas ; Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ferring; Speaker Bureau / Expert testimony: GSK; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Janssen; Research grant / Funding (institution): MDX Health; Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: Sanofi. J. Bellmunt: Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution): Takeda; Shareholder / Stockholder / Stock options: Biocline. All other authors have declared no conflicts of interest.

Aim: The Chemotherapy and Pharmacy Advisory Service (CPAS) was established in 2007 by the UK National Cancer Research Network (NCRN) to improve the quality of pharmacy-related issues in clinical research protocols. We report the scope and methodology of the CPAS, and its impact on the quality of clinical research protocols. Methods: All clinical research protocols were independently reviewed by a minimum of three health professionals including at least one oncology pharmacist, using a customised protocol review checklist (assessing 12 areas of clinical oncology/pharmacy). A collated review was subsequently drafted by the CPAS pharmacy advisor and returned to the chief investigators. A working party performed a systematic review of all protocol reviews conducted by CPAS during the 6-year period since its inception (2008-2013) and categorised the remarks. A service evaluation audit was conducted to check response rate and acceptance rate of the proposed changes with chief investigators. Results: During the 6 year systematic review period a total of 176 clinical research protocols were reviewed. The median number of remarks per protocol was 26 of which 20 were deemed clinically relevant. The majority of clinically relevant remarks concerned the drug regimen, guidelines concerning support medication, frequency and type of monitoring and drug supply aspects. Further analysis of the 176 protocols reviewed revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. Conclusions: Review of pharmacy aspects regarding clinical cancer research protocols is feasible and reveals many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the very large majority of suggestions were effectively incorporated in the final protocols. Disclosure: All authors have declared no conflicts of interest.