STAMPEDE trial

STAMPEDE trial
Name	STAMPEDE
Acronym	STAMPEDE
Phase	III
Start date	2005
Countries	United Kingdom, Switzerland
Participants	>8,000
Conditions	Prostate cancer
Interventions	Hormone therapy, chemotherapy, radiotherapy, targeted agents

STAMPEDE trial

The STAMPEDE trial was a large, multiarm, multistage randomized controlled trial for advanced and high‑risk prostate cancer funded and coordinated by the Medical Research Council (United Kingdom), conducted at centers including University College London Hospitals NHS Foundation Trust, The Institute of Cancer Research, and Royal Marsden NHS Foundation Trust, and involving collaborators such as Cancer Research UK and National Institute for Health and Care Research. Designed to evaluate systemic therapies added to androgen‑deprivation, STAMPEDE enrolled patients across the United Kingdom, with participating sites linked to networks including the National Health Service and international partners such as Swiss Group for Clinical Cancer Research. Results have influenced guidelines from bodies like the European Society for Medical Oncology and the National Comprehensive Cancer Network.

Background

STAMPEDE originated amid evolving evidence from pivotal trials like CHAARTED, GETUG-AFU 15, and earlier studies at institutions including Memorial Sloan Kettering Cancer Center, prompting collaboration between investigators at University of Oxford, University of Cambridge, and University of Glasgow to address unmet needs in metastatic and high‑risk nonmetastatic prostate cancer. The platform incorporated learnings from landmark randomized trials such as PROSPER (trial), SPARTAN (trial), and hormone therapy research at Mayo Clinic while engaging regulatory stakeholders including the European Medicines Agency and the Food and Drug Administration. Trial leadership included clinicians affiliated with Royal College of Surgeons of England and methodology advisors from London School of Hygiene & Tropical Medicine.

Trial design and methods

STAMPEDE used a multiarm, multistage adaptive platform design developed with statisticians from University of Birmingham, integrating interim analyses and seamless phase transitions informed by frameworks from Clinical Trials Unit at The Institute of Cancer Research and University of Manchester. Randomization schemes employed centralized allocation overseen by data monitoring committees akin to those at Johns Hopkins Medicine and Dana‑Farber Cancer Institute, with endpoints including overall survival and failure‑free survival comparable to outcomes used in trials at Vanderbilt University Medical Center and Fred Hutchinson Cancer Research Center. Imaging and biomarker assessments referenced standards from Royal College of Radiologists and laboratory collaborations with Public Health England and Addenbrooke's Hospital.

Interventions and treatment arms

STAMPEDE evaluated addition of systemic agents to androgen‑deprivation therapy, comparing control arms to experimental arms testing agents endorsed or studied by institutions like AstraZeneca, GlaxoSmithKline, and Janssen Pharmaceuticals. Key comparisons included docetaxel chemotherapy (drawing on protocols from National Cancer Institute collaborations), androgen receptor pathway inhibitors such as abiraterone acetate (as studied at Institut Gustave Roussy) and enzalutamide (researched at Vanderbilt University), and biologics including zoledronic acid (from University of Michigan) and radiotherapy integration modeled after trials at Princess Margaret Cancer Centre. Additional arms tested celecoxib and other repurposed agents informed by work at Karolinska Institutet and University of Sydney.

Outcomes and results

Major STAMPEDE publications reported significant overall survival benefits for adding therapies such as docetaxel and abiraterone to androgen‑deprivation, with outcome reporting influenced by statistical approaches from Cochrane Collaboration methodologies and trial reporting standards used by The Lancet Oncology and New England Journal of Medicine. Findings paralleled results from CHAARTED and extended observations from GETUG-AFU 15, demonstrating improvements in progression‑free survival and metastatic control similar to those reported at MD Anderson Cancer Center and Hospital Clínic de Barcelona. Results also informed cost‑effectiveness analyses performed by groups at Imperial College London and policy assessments by NICE.

Subgroup and secondary analyses

Preplanned subgroup analyses explored heterogeneity by metastatic burden, age, and performance status, using analytic methods developed in collaboration with statisticians at University of Edinburgh and University of Leeds. Secondary publications examined quality of life using instruments validated by European Organisation for Research and Treatment of Cancer and health economics outcomes with frameworks from Office for National Statistics research. Ancillary biomarker studies involved partners from Wellcome Trust Sanger Institute and tissue banks at Addenbrooke's Hospital, enabling correlative analyses akin to translational programs at Broad Institute.

Impact on clinical practice and guidelines

STAMPEDE influenced international guideline recommendations from organizations such as the European Association of Urology, American Urological Association, ASCO and NICE, prompting wider adoption of early systemic intensification for selected patients, integration of radiotherapy in node‑negative high‑risk settings, and consideration of combination strategies discussed at meetings of the American Society of Clinical Oncology and European Society for Radiotherapy and Oncology. Health systems including the NHS England and payers across Canada, Australia, and Germany referenced STAMPEDE evidence in coverage and care pathways, reshaping standard‑of‑care approaches in tertiary centers like Guy's and St Thomas' NHS Foundation Trust and influencing ongoing platform trials at institutions such as Fred Hutchinson Cancer Research Center and Memorial Sloan Kettering Cancer Center.

Category:Clinical trials