{"entity":{"id":"stampede","kind":"trial","name":"STAMPEDE","aka":["STAMPEDE trial","MRC PR08","Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy","STAMPEDE platform"],"tldr":"STAMPEDE is the longest-running platform trial in oncology, and showed that both docetaxel and abiraterone extend life when started at first diagnosis of metastatic disease.","summary":"STAMPEDE opened in 2005 at the MRC Clinical Trials Unit at UCL, with Nicholas James as chief investigator and Mahesh Parmar as its statistician, as the first multi-arm multi-stage trial in cancer: several experimental arms recruited at once against one control arm of androgen deprivation therapy, each passing through interim activity stages before being allowed to continue to an overall survival comparison, with new arms added and failing arms dropped as the standard of care moved. Nearly 12,000 men with high-risk locally advanced or newly metastatic prostate cancer joined at more than 100 hospitals in the United Kingdom and Switzerland; Silke Gillessen led the Swiss contribution and later co-chaired the trial. The original arms added zoledronic acid, docetaxel, celecoxib and their combinations; the celecoxib arms were stopped for lack of activity in 2011, and abiraterone (2011), radiotherapy to the prostate (2013), abiraterone with enzalutamide (2014), metformin (2016) and transdermal oestradiol (run jointly with the PATCH trial) were added.\n\nThe results arrived in sequence and each changed practice. In 2016 the Lancet reported that docetaxel added to hormone therapy improved overall survival, most clearly in metastatic disease, while zoledronic acid added nothing; the finding replicated CHAARTED and made early chemotherapy a standard. In 2017 the New England Journal of Medicine reported, alongside LATITUDE, that abiraterone with prednisolone cut the risk of death by about a third (hazard ratio 0.63), which established abiraterone at first diagnosis of metastatic disease. In 2018 the Lancet reported that radiotherapy to the prostate improved survival in men with a low metastatic burden but not overall, and low-volume prostate radiotherapy entered guidelines. In 2022 the Lancet reported that two years of abiraterone improved metastasis-free and overall survival in high-risk non-metastatic disease, and that adding enzalutamide brought toxicity without benefit; the Lancet Oncology in 2023 confirmed the same for enzalutamide in metastatic disease. The metformin comparison, reported at ESMO in 2024 and since published, found no overall survival benefit from adding metformin for men starting hormone therapy for metastatic disease. The transdermal oestradiol comparison, run with PATCH, showed that oestrogen patches suppress testosterone as well as injections with fewer hot flushes, better bone health and no excess of cardiovascular events (Lancet 2021).\n\nSTAMPEDE is the proof that a single academic platform with a shared control arm can answer a decade of questions faster and more cheaply than separate trials, and its multi-arm multi-stage design is now used across cancer and beyond. Its weaknesses are the ones every platform inherits: the control arm changed as docetaxel and then abiraterone became standard, so later arms were compared with a moving baseline, and some comparisons (radiotherapy, enzalutamide) were read in subgroups defined after the fact. The successor, STAMPEDE2, opened in 2023 with comparisons of stereotactic radiotherapy to metastases, lutetium PSMA radioligand therapy and niraparib with abiraterone in men starting treatment for metastatic disease.","status":"positive","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT00268476","url":"https://clinicaltrials.gov/study/NCT00268476"},{"label":"James et al., Lancet 2016: addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE)","url":"https://doi.org/10.1016/S0140-6736(15)01037-5"},{"label":"James et al., NEJM 2017: abiraterone for prostate cancer not previously treated with hormone therapy (STAMPEDE)","url":"https://doi.org/10.1056/NEJMoa1702900"},{"label":"Parker et al., Lancet 2018: radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE)","url":"https://doi.org/10.1016/S0140-6736(18)32486-3"},{"label":"Attard et al., Lancet 2022: abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer (STAMPEDE)","url":"https://doi.org/10.1016/S0140-6736(21)02437-5"},{"label":"Attard et al., Lancet Oncology 2023: abiraterone plus prednisolone with or without enzalutamide for metastatic prostate cancer starting ADT (STAMPEDE)","url":"https://doi.org/10.1016/S1470-2045(23)00148-1"},{"label":"Langley et al., Lancet 2021: transdermal oestradiol for androgen suppression in prostate cancer, long-term cardiovascular outcomes from PATCH","url":"https://doi.org/10.1016/S0140-6736(21)00100-8"},{"label":"STAMPEDE trial website (MRC CTU at UCL)","url":"https://www.stampedetrial.org"}],"tags":[],"related":[],"indications":["prostate","prostate-mhspc","prostate-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","docetaxel","enzalutamide"],"companies":[],"institutions":["royal-marsden"],"pathways":[],"terms":["mcrpc-mhspc"],"trials":[],"people":["silke-gillessen"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00268476","phase":"platform","setting":"Multi-arm multi-stage platform in men starting long-term hormone therapy for high-risk locally advanced or metastatic prostate cancer: docetaxel, zoledronic acid, celecoxib, abiraterone, radiotherapy to the prostate, abiraterone with enzalutamide, metformin and transdermal oestradiol added to ADT and compared with ADT alone","sponsor":"MRC Clinical Trials Unit at UCL, funded by Cancer Research UK and the Medical Research Council","result":"Abiraterone + ADT: OS HR 0.63 in mHSPC; docetaxel + ADT: OS HR 0.78. Prostate radiotherapy improved survival in low-volume metastatic disease; abiraterone improved survival in high-risk non-metastatic disease; enzalutamide added to abiraterone, zoledronic acid, celecoxib and metformin did not improve survival.","yearReported":2016,"enrolled":11992,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, abiraterone arm (M1 subgroup)","primary":true,"unit":"%","arms":[{"name":"ADT + abiraterone","note":"6-year OS 60%"},{"name":"ADT alone","note":"6-year OS 45%"}],"hr":0.6,"ci":[0.5,0.71],"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00367-1/fulltext"},{"endpoint":"Overall survival, docetaxel arm (M1)","unit":"months","arms":[{"name":"ADT + docetaxel","value":60},{"name":"ADT alone","value":45}],"hr":0.76,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01037-5/fulltext"}],"replication":"Abiraterone result replicated by LATITUDE; docetaxel result replicated by CHAARTED."},"route":"/trials/stampede/","neighbours":{"indication":[{"id":"prostate-high-risk","kind":"indication","name":"Localised prostate cancer, high and very high risk","route":"/indications/prostate-high-risk/"},{"id":"prostate-mhspc","kind":"indication","name":"Metastatic hormone-sensitive prostate cancer","route":"/indications/prostate-mhspc/"},{"id":"prostate","kind":"indication","name":"Prostate cancer","route":"/indications/prostate/"}],"drug":[{"id":"abiraterone","kind":"drug","name":"Abiraterone acetate","route":"/drugs/abiraterone/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"}],"institution":[{"id":"royal-marsden","kind":"institution","name":"The Royal Marsden","route":"/institutions/royal-marsden/"}],"term":[{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","route":"/terms/mcrpc-mhspc/"}],"person":[{"id":"silke-gillessen","kind":"person","name":"Silke Gillessen","route":"/people/silke-gillessen/"}]}}