of potential adverse cardiovascular eff No safety concerns were raised during the pilot phase and the first intermediate activity analysis, and the celecoxib arms were permitted to continue accrual. Here, we report the results of the second intermediate analysis comparing hormone therapy alone with hormone therapy plus celecoxib. STAMPEDE uses an adaptive multiarm, multistage Everolimus design, This seamless phase design starts with several trial arms and uses an intermediate outcome to adaptively focus accrual away from the less encouraging research arms, continuing accrual only with the more active interventions. The definitive primary outcome of the STAMPEDE trial is overall survival.
The intermediate Salinomycin inhibitor primary outcome is failure-free survival defi ned as the first of: PSA failure; local progression; nodal progression; progression of existing metastases or development of new metastases; or death from prostate cancer. FFS is used as a screening method for activity on the assumption that any treatment that shows an advantage in overall survival will probably show an advantage in FFS beforehand, and that a survival Tofacitinib JAK inhibitor advantage is unlikely if an advantage in FFS is not seen. Therefore, FFS can be used to triage treatments that are unlikely to be of suffi cient benefit. It is not assumed that FFS is a surrogate for overall survival; an advantage in FFS might not necessarily translate into a survival advantage. The trial is managed by a trial management group chaired by the chief investigator.
Accumulating comparative data are reviewed by the independent data monitoring committee and recommendations buy Hematoxylin are made to the trial steering committee, which includes independent members, who have the fi nal responsibility for decision making, on stopping arms). The TSC can view limited accumulating comparative trial data to take appropriate action. Patients were recruited from specialist centres with the appropriate local and national approvals. The eligibility criteria encompassed a range of patients requiring treatment with long-term hormone therapy. We postulated that the relative effect of the research treatments would be the same across trial arms, even if the absolute event rate differed. We included patients with newly diagnosed prostate cancer with metastases to bone, node-positive disease, or clinically localised disease with high-risk features.
Additionally, men failing previous localised therapy higher and doubling time of less than 6 months, or PSA 20 ng/mL or higher, or nodal or metastatic relapse. Patients had to be fit for any of the trial treatments, with adequate haematological, renal, and liver function, and have a WHO performance status. Patients social roles with a confirmed history of severe cardiovascular problems, active peptic ulceration, gastrointestinal bleeding, or inflammatory bowel disease were excluded. All patients provided written informed consent. Randomisation and masking Computer-based randomisation was done centrally using minimisation with a random element of allocation towards minimising arms, balancing on minimisation factors of randomising centre, metastases, nodal involvement, age at randomisation, WHO performance status, type of hormone therapy, regular aspirin or NSAID use at baseline, and planned use of radiotherapy. Patients could be allocated All patients were planned to receive long-term hormone therapy for at least 2 years, and were allowed to start long- term hormone therapy up to 12 weeks before randomisation.