title: Systemic therapy for advancing or metastatic prostate cancer (STAMPEDE): a multi-arm, multistage randomized controlled trial.
abstract: There is a need to improve the outcomes for men with high-risk localised, nodal or metastatic prostate cancer, or with aggressively relapsing disease after initial therapy for local disease. This group of men is currently managed with long-term hormone therapy. Thus we aim to evaluate the toxicity and efficacy of three different systemic therapies (docetaxel, zoledronic acid and celecoxib) used alone or combined at the initiation of hormone manipulation for high-risk prostate cancer. A novel statistical design (multi-arm, multistage method) simultaneously tests multiple distinct strategies in parallel against a single control arm. The trial has several 'stages', from initial confirmation of safety to a phase III assessment of survival, with a series of intervening activity stages. This method provides a means of assessing several agents more quickly and efficiently, and allows inactive treatments to be dropped from further study at an early stage. STAMPEDE has been designed to address in parallel the activity and efficacy of these agents for this patient group. It is a flagship randomized clinical trial for academic research into prostate cancer in the UK. More than 500 patients have been recruited on schedule, confirming the acceptability of this complex trial design to patients and clinicians. The trial targets a population of approximately 3000 patients. STAMPEDE is a major new trial with a novel design applicable to the synchronous testing of several agents. It is hoped that the results will improve outcomes for patients with high-risk prostate cancer. The design could be applicable to the study of new therapies in other cancer types. Continued efforts are required by the urological cancer community to maintain the excellent recruitment shown to date.
authors.affiliation: CRUK Institute for Cancer Studies, University of Birmingham, UK.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: James
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Sydes
authors.forename: Noel W
authors.initials: NW
authors.lastname: Clarke
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: John
authors.initials: J
authors.lastname: Anderson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Popert
authors.forename: Karen
authors.initials: K
authors.lastname: Sanders
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Morgan
authors.forename: Jim
authors.initials: J
authors.lastname: Stansfeld
authors.forename: John
authors.initials: J
authors.lastname: Dwyer
authors.forename: John
authors.initials: J
authors.lastname: Masters
authors.forename: Mahesh K B
authors.initials: MK
authors.lastname: Parmar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068579:Celecoxib; D004164:Diphosphonates / Q000008:administration & dosage; D000077143:Docetaxel; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D011720:Pyrazoles; D013449:Sulfonamides; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid; D000068579:Celecoxib