# STAMPEDE

Source: https://onco.cc/trials/stampede/  
OnCo record `stampede` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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).

STAMPEDE 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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Also known as: STAMPEDE trial; MRC PR08; Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy; STAMPEDE platform
- Registry id: 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
- Enrolled: 11992
- 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.
- Outcomes: Overall survival, abiraterone arm (M1 subgroup): ADT + abiraterone vs ADT alone, HR 0.6; Overall survival, docetaxel arm (M1): ADT + docetaxel 60 months vs ADT alone 45 months, HR 0.76; Overall survival, abiraterone comparison: Androgen deprivation with abiraterone and prednisolone 184 deaths vs Androgen deprivation alone 262 deaths, HR 0.63; Metastasis-free survival at 6 years, high-risk non-metastatic comparison: Androgen deprivation with 2 years of abiraterone 82% vs Androgen deprivation alone 69%, HR 0.53; Overall survival, prostate radiotherapy comparison: Standard of care with prostate radiotherapy vs Standard of care, HR 0.92; Overall survival (median), metformin comparison: Standard of care with metformin 67.4 months vs Standard of care 61.8 months, HR 0.91
- Replication: Abiraterone result replicated by LATITUDE; docetaxel result replicated by CHAARTED.

## Notes

- The STAMPEDE metformin comparison, reported in Lancet Oncology in 2025, randomised 1,874 men with metastatic disease and no diabetes (HbA1c below 48 mmol/mol) and adequate renal function to standard of care or standard of care plus metformin 850 mg twice daily. Standard of care was androgen deprivation with or without radiotherapy and with or without docetaxel or an androgen receptor pathway inhibitor; 1,543 of 1,874 (82 percent) received docetaxel and 52 (3 percent) an androgen receptor pathway inhibitor. At a median 60 months of follow-up there were 473 deaths on standard of care (median survival 61.8 months) and 453 with metformin (67.4 months), hazard ratio 0.91 (95 percent confidence interval 0.80 to 1.03, p=0.15). Grade 3 or worse adverse events occurred in 52 percent against 57 percent, the excess being gastrointestinal. There were six drug-related deaths on standard of care and one with metformin.
- The high-risk non-metastatic comparison, reported in the Lancet in 2022 as a meta-analysis of two STAMPEDE randomisations in 1,974 men at 113 sites in the United Kingdom and Switzerland, found metastasis-free survival significantly longer with 2 years of abiraterone added to 3 years of androgen deprivation, hazard ratio 0.53 (95 percent confidence interval 0.44 to 0.64, p<0.0001), with 6-year metastasis-free survival 82 percent (79 to 85) against 69 percent (66 to 72). Adding enzalutamide to abiraterone gave no further benefit (interaction hazard ratio 1.02, 0.70 to 1.50, p=0.91) and no between-trial heterogeneity was seen. Median age was 68, median PSA 34 ng/mL, 39 percent were node positive and 85 percent were planned to receive radiotherapy.
- The prostate radiotherapy comparison randomised 2,061 men with newly diagnosed metastatic disease at 117 hospitals between 22 January 2013 and 2 September 2016. Failure-free survival improved (hazard ratio 0.76, 95 percent confidence interval 0.68 to 0.84, p<0.0001) but overall survival did not (0.92, 0.80 to 1.06, p=0.266). Forty percent had low metastatic burden and 54 percent high. Radiotherapy was well tolerated, with 48 men (5 percent) reporting RTOG grade 3 to 4 events during radiotherapy and 37 (4 percent) after it.

## Sources

- ClinicalTrials.gov NCT00268476: https://clinicaltrials.gov/study/NCT00268476
- James et al., Lancet 2016: addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): https://doi.org/10.1016/S0140-6736(15)01037-5
- James et al., NEJM 2017: abiraterone for prostate cancer not previously treated with hormone therapy (STAMPEDE): https://doi.org/10.1056/NEJMoa1702900
- Parker et al., Lancet 2018: radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): https://doi.org/10.1016/S0140-6736(18)32486-3
- Attard et al., Lancet 2022: abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer (STAMPEDE): https://doi.org/10.1016/S0140-6736(21)02437-5
- Attard et al., Lancet Oncology 2023: abiraterone plus prednisolone with or without enzalutamide for metastatic prostate cancer starting ADT (STAMPEDE): https://doi.org/10.1016/S1470-2045(23)00148-1
- Langley et al., Lancet 2021: transdermal oestradiol for androgen suppression in prostate cancer, long-term cardiovascular outcomes from PATCH: https://doi.org/10.1016/S0140-6736(21)00100-8
- STAMPEDE trial website (MRC CTU at UCL): https://www.stampedetrial.org
- STAMPEDE metformin (Lancet Oncology 2025): https://doi.org/10.1016/S1470-2045(25)00231-1

## Connected records

- cancers: [Localised prostate cancer, high and very high risk](https://onco.cc/cancers/prostate-high-risk/), [Metastatic hormone-sensitive prostate cancer](https://onco.cc/cancers/prostate-mhspc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)
- drugs: [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Celecoxib](https://onco.cc/drugs/celecoxib/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Zoledronic acid](https://onco.cc/drugs/zoledronic-acid/)
- companies: [MRC Clinical Trials Unit at UCL](https://onco.cc/companies/mrc-ctu/)
- institutions: [Cancer Research UK](https://onco.cc/institutions/cruk/), [The Institute of Cancer Research](https://onco.cc/institutions/icr-london/), [The Royal Marsden](https://onco.cc/institutions/royal-marsden/), [University College London Hospitals / UCL Cancer Institute](https://onco.cc/institutions/uclh/)
- terms: [Basket, umbrella, and platform trials](https://onco.cc/terms/basket-umbrella-platform/), [Interim analysis, readout and data cut-off](https://onco.cc/terms/interim-analysis/), [Master protocol (platform, basket and umbrella trials)](https://onco.cc/terms/master-protocol/), [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://onco.cc/terms/mcrpc-mhspc/), [Response-adaptive randomisation](https://onco.cc/terms/response-adaptive-randomisation/), [Seamless, adaptive and Bayesian trial designs](https://onco.cc/terms/seamless-adaptive/), [STAMPEDE's arms, and what each one answered](https://onco.cc/terms/prostate-stampede-arms/), [Umbrella trial](https://onco.cc/terms/umbrella-trial/)
- trials: [CHAARTED (E3805)](https://onco.cc/trials/chaarted/), [GETUG-AFU 15](https://onco.cc/trials/getug-afu-15/), [HORRAD](https://onco.cc/trials/horrad/), [LATITUDE](https://onco.cc/trials/latitude/), [NRG Oncology RTOG 0521](https://onco.cc/trials/rtog-0521/), [PATCH (Prostate Adenocarcinoma Transcutaneous Hormone)](https://onco.cc/trials/patch-transdermal-oestradiol/)
- people: [Gerhardt Attard](https://onco.cc/people/gerhardt-attard/), [Mahesh K. B. Parmar](https://onco.cc/people/mahesh-parmar/), [Nicholas James](https://onco.cc/people/nicholas-james/), [Silke Gillessen](https://onco.cc/people/silke-gillessen/)
- key papers: [Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol](https://onco.cc/key-papers/paper-attard-lancet-oncol/), [Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial](https://onco.cc/key-papers/paper-stampede-lancet-2016/), [Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial](https://onco.cc/key-papers/paper-parker-lancet/), [Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial](https://onco.cc/key-papers/paper-stampede-plos-med-2022-update/), [STAMPEDE: abiraterone with or without enzalutamide added to androgen deprivation for high-risk non-metastatic prostate cancer](https://onco.cc/key-papers/paper-stampede-abiraterone-high-risk-attard-lancet-2022/), [Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme](https://onco.cc/key-papers/paper-langley-lancet/)
- bottlenecks: [Too many combinations to test](https://onco.cc/bottlenecks/b-combination-space/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- ideas: [A perpetual platform trial in every major cancer, funded as infrastructure](https://onco.cc/ideas/idea-tr2-perpetual-platforms/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/), [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)

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