title: The STAR trial protocol: a randomised multi-stage phase II/III study of Sunitinib comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced/metastatic renal cancer.
abstract: BACKGROUND
  Over recent years a number of novel therapies have shown promise in advanced renal cell carcinoma (RCC). Internationally the standard of care of first-line therapy is sunitinib™, after a clear survival benefit was demonstrated over interferon-α. Convention dictates that sunitinib is continued until evidence of disease progression, assuming tolerability, although there is no evidence that this approach is superior to intermittent periods of treatment. The purpose of the STAR trial is to compare the standard treatment strategy (conventional continuation strategy, CCS) with a novel drug free interval strategy (DFIS) which includes planned treatment breaks.
  
  
  METHODS
  The STAR trial is an NIHR HTA-funded UK pragmatic randomised phase II/III clinical trial in the first-line treatment of advanced RCC. Participants will be randomised (1:1) to either a sunitinib CCS or a DFIS. The overall aim of the trial is to determine whether a DFIS is non-inferior, in terms of 2-year overall survival (OS) and quality adjusted life years (QALY) (averaged over treatment and follow up), compared to a CCS. The QALY primary endpoint was selected to assess whether any detriment in terms of OS could be balanced with improvements in quality of life (QoL). This is a complex trial with a number of design challenges, and to address these issues a feasibility stage is incorporated into the trial design. Predetermined recruitment (stage A) and efficacy (stage B) intermediary endpoints must be met to allow continuation to the overall phase III trial (stage C). An integral qualitative patient preference and understanding study will occur alongside the feasibility stage to investigate patients' feelings regarding participation or non-participation in the trial.
  
  
  CONCLUSIONS
  The optimal duration of continuing sunitinib in advanced RCC is unknown. Novel targeted therapies do not always have the same constraints to treatment duration as standard chemotherapeutic agents and currently there are no randomised data comparing different treatment durations. Incorporating planned treatment breaks has the potential to improve QoL and cost effectiveness, hopefully without significant detriment on OS, as has been demonstrated in other cancer types with other treatments.
  
  
  BACKGROUND
  Controlled-trials.com ISRCTN 06473203.
authors.affiliation: Clinical Trials Research Unit, University of Leeds, and Department of Radiology, St James's University Hospital, Leeds LS2 9JT, UK.
authors.forename: Fiona J
authors.initials: FJ
authors.lastname: Collinson
authors.forename: Walter M
authors.initials: WM
authors.lastname: Gregory
authors.forename: Chris
authors.initials: C
authors.lastname: McCabe
authors.forename: Helen
authors.initials: H
authors.lastname: Howard
authors.forename: Catherine
authors.initials: C
authors.lastname: Lowe
authors.forename: DrBarbara
authors.initials: D
authors.lastname: Potrata
authors.forename: Sandy
authors.initials: S
authors.lastname: Tubeuf
authors.forename: Pat
authors.initials: P
authors.lastname: Hanlon
authors.forename: Lucy
authors.initials: L
authors.lastname: McParland
authors.forename: T
authors.initials: T
authors.lastname: Wah
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Selby
authors.forename: Jenny
authors.initials: J
authors.lastname: Hewison
authors.forename: Julia
authors.initials: J
authors.lastname: Brown
authors.forename: Janet
authors.initials: J
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D007211:Indoles / Q000191:economics / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000191:economics / Q000627:therapeutic use*; D011758:Pyrroles / Q000191:economics / Q000627:therapeutic use*; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D000077210:Sunitinib; D016019:Survival Analysis; D006113:United Kingdom; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib