Lack of treatments and evidence

As recently as ten years ago, despite many new drugs being approved for use in prostate cancer, many men with high-risk disease still had insufficient treatment options and it was unclear how well drugs work in this population. Prior to the STAMPEDE trial the standard of care for prostate cancer had not changed for many decades.

To address this challenge to the treatment of high-risk prostate cancer, researchers from MRC Clinical Trials Unit at UCL brought an idea to test a variety of current treatments in men with high-risk prostate cancer to the NCRI Prostate Group.

Innovation in trial design

Within the group, the researchers developed a plan to implement an innovative trial design – it was a multi-arm, multi-stage design that would allow them to test a greater number of treatments faster and more efficiently. The STAMPEDE trial would have only one ‘control’ arm, against which all other treatments could be tested, and there were analysis periods built in so that insufficiently active treatments could be stopped rather than continued to the end of the trial.

Table: Treatment comparisons investigated at times across the STAMPEDE trial

Standard of care alone
Standard of care plus zoledronic acid (normally used to treat cancers that have spread to the bone)
Standard of care plus docetaxel chemotherapy
Standard of care plus celecoxib (a cyclooxygenase, Cox-2, inhibitor)
Standard of care plus zoledronic acid + docetaxel
Standard of care plus zoledronic acid + celecoxib
Standard of care plus abiraterone (a steroid synthesis inhibitor)
Standard of care plus abiraterone + enzalutamide (an inhibitor of androgen receptor signalling)
Standard of care plus the provision of prostate radiotherapy for men with metastases
Standard of care plus metformin (a drug that lowers blood sugar levels)
Standard of care plus transdermal oestradiol (an alternative way to give hormone therapy)

*Standard of care was long-term hormone therapy, plus radiotherapy if possible, in non-metastatic patients. The standard has been updated over time to include docetaxel or abiraterone, and radiotherapy across all patients

By testing multiple treatments at once the study required fewer participants and was faster than running several consecutive trials, allowing benefits to reach patients earlier. The trial was also more efficient and less costly than running several concurrent trials.

The NCRI Prostate Group provided essential input into the clinical design and practical implementation of the trial, with oncologists, urologists, statisticians and operations specialists working together. The group continues to contribute to the trial’s ongoing development. Each of the NCRI Groups provide a unique perspective on their research area, and, in the STAMPEDE trial, the NCRI Prostate Group ensure that new research ideas are proposed for incorporation into and testing in the trial where appropriate. This prevents the set-up of multiple competing trials that could hinder recruitment and slow progress.

Benefiting patients with high-risk disease

To date, the results of seven treatments tested in this trial have been published. Three of those were found to be of benefit to men with high-risk prostate cancer.

  • The addition of docetaxel was shown to improve survival, results published in The Lancet
  • The addition of abiraterone to androgen-deprivation therapy was shown to improve survival, results published in the New England Journal of Medicine
  • The provision of radiotherapy to patients with metastatic prostate cancer, resulted in a substantial improvement in survival for some men, results published in The Lancet

The findings from this trial are now being translated into practice, with docetaxel now available on the NHS as an additional treatment for men with metastatic prostate cancer.

Without this trial design, and the NCRI Prostate Group that helped to develop it, it would have taken significantly longer to test these treatments, and the trials would have been more expensive. This study has changed the way that prostate cancer studies are run because of its effectiveness, with new studies including one set up by Professor Hashim Ahmed, chair of the NCRI Prostate Group investigating the use of focal therapy in men diagnosed with significant cancer confined to the prostate, based on this study design.