Emphasising the importance of such collaboration in the design and conduct of clinical trials

for all other trial arms were reviewed by the IDMC but were not released for further review. These data, including those for the hormone therapy plus celecoxib plus zoledronic acid group, remain confidential to the Pazopanib IDMC and will only be available to the TSC after future analyses. In the STAMPEDE trial, we are assessing several drugs in combination with hormone therapy in patients with high-risk localised or metastatic prostate cancer. Resources are focused on trial arms most likely to show a clinically meaningful survival benefit by using intermediate lack-of-benefit analyses and stopping accrual to arms showing insufficient activity or adverse safety profi les. The celecoxib arm continued accrual through the fi rst intermediate analysis, but accrual was stopped after the second intermediate analysis when the target HR was more difficult to pass, at 0·92.
Recruitment to the hormone therapy plus celecoxib group was stopped with immediate effect. Although Sinomenine inhibitor there were no safety concerns raised by the IDMC, there was no evidence of benefit when the totality of the data were taken into consideration, and the TSC recommended that treatment with celecoxib stop for patients still receiving the drug. Our premise is that an advantage in overall survival should be preceded by an advantage in FFS, so we do not anticipate a later benefit with celecoxib emerging; however, this remains to be determined in subsequent analysis of overall survival Hesperidin 520-26-3 after longer follow-up. In some CRPC studies this assumption has not held up, particularly studies with the immunotherapy sipuleucel-T, where a survival advantage has been shown without a prior benefi t in PSA progression.
10 The potential mechanisms of action of celecoxib are not androgen-linked, so it is reasonable to assume that they might not be reflected in PSA-based measures of FFS; on this basis, we continue long-term patient follow-up and avoid definitive statements relating buy Elvitegravir to the overall efficacy of COX-2 inhibition and prostate- cancer survival in this setting. Recruitment was also stopped to the hormone therapy plus celecoxib plus zoledronic acid group; data for this arm have not been revealed to avoid inappropriate influence on recruitment in the other zoledronic acid- containing arms. These data will subsequently become available, giving further information from an additional 450 patients randomised to receive celecoxib as part of treatment.
The patients in both celecoxib-containing groups remain in the trial occupation and will continue to be followed up to provide data on overall survival. Subgroup analyses by disease stage were done but not made available for reporting. The IDMC charter allows it to make recommendations within a subgroup if warranted by the data. There would have been limited power for such a comparison at this stage. Celecoxib, a selective COX-2 inhibitor, was selected on the basis of preclinical13,14,19 and clinical16–18 data suggesting possible utility in prostate cancer The celecoxib dose and treatment duration chosen for the trial was based on the dose used for prevention of familial polyposis coli20 and the need to minimise potential for cardiovascular risk, which seems to present with treatment durations longer than 12 months.21 The dose and duration were selected after a comprehensive literature review followed by joint discussion with patient representatives on the TMG, emphasising the importance of such collaboration in the design and conduct of clinical trials.

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