A Randomised Controlled Platform Trial Testing Treatments in Metastatic Hormone Sensitive Prostate Cancer
STAMPEDE2
Studying Treatments in Patients Receiving Androgen Deprivation Therapy (ADT) for Metastatic Prostate Cancer: Evaluation of Drug and Radiation Efficacy: A 2nd Multi-arm Multi-stage Randomised Controlled Trial (STAMPEDE2).
2 other identifiers
interventional
3,360
1 country
18
Brief Summary
STAMPEDE2 is a clinical trial comparing two new treatments with standard of care in people with prostate cancer that has spread to other parts of the body and is responsive to hormone therapy. People from all backgrounds and ethnicities are encouraged to take part and multiple hospitals across the UK are involved. University College London is running the trial. Each comparison within the trial has its own control arm where people get the best standard of care (Arm A) versus a research arm where a new treatment is added to standard of care. Participants are allocated to an arm by a computerised system with a 50% chance of getting the research treatment. Comparison S: Arm A versus Arm S (Stereotactic Ablative Body Radiotherapy (SABR)) - Tests whether giving targeted doses of radiotherapy (SABR) to parts of the body where the cancer has spread slows the spread of the cancer and improves survival. 2476 people will be in this comparison. Comparison P: Arm A versus Arm P (PSMA-Lutetium (177Lu-PSMA-617)) - Tests whether giving a radioactive material (177Lu-PSMA-617) that targets prostate cancer cells slows the spread of the cancer and improves survival. 1756 people will be in this comparison. All participants will be followed up with scans and tests to monitor their cancer. Doctors will check for any side effects from the treatments. Treatments will be stopped if side effects are serious, or people no longer wish to take the treatments.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2024
Longer than P75 for phase_3
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 10, 2024
CompletedFirst Posted
Study publicly available on registry
March 20, 2024
CompletedStudy Start
First participant enrolled
June 11, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2032
September 26, 2025
September 1, 2025
6.8 years
January 10, 2024
September 22, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
OS is defined as time from randomisation to death from any cause. The final reporting times of OS for each comparison below will depend on the recruitment rates and the accuracy of assumed median survival times in the sample size calculations.
Final analysis for each comparison triggered when adequate number of death events have occurred in control arm of each comparison. Anticipate final reporting for OS in Comparison S: ~84 months (7 years) from FPFV, P: ~64 months (5.3 years) from FPFV.
Secondary Outcomes (8)
Failure-Free Survival (FFS)
Up to 10 years from randomisation. FFS is declared as a secondary outcome and is not part of sample size calculations, nor timelines for the study.
Radiographic Progression-Free-Survival (rPFS)
Up to 10 years from randomisation. rPFS is declared as a secondary outcome and is not part of sample size calculations, nor timelines for the study.
Prostate cancer specific survival (PCSS)
Up to 10 years from randomisation. PCSS is declared as a secondary outcome and is not part of the sample size calculations, nor timelines for the study.
Safety through reporting of SAEs
S: until 6 months after randomisation; P: until 6 months after randomisation or 40 days after completion or permanent discontinuation of an IMP 177Lu-PSMA-617 (whichever is furthest); N: until 30 days after permanent discontinuation of an IMP
Toxicity using CTCAE classification and reporting of all Adverse Events that are ≥ grade 3 or grade 1 and 2 leading to a change in trial treatment
All safety and toxicity data will be presented by randomised group. The exact nature of this will be pre-specified in the statistical analysis plan that is still in development.
- +3 more secondary outcomes
Study Arms (4)
Arm A of SABR Comparison
ACTIVE COMPARATORSoC (ADT + ARPI ± docetaxel + local RT)
Arm S of SABR Comparison
EXPERIMENTALSoC (ADT + ARPI ± docetaxel + local RT) + SABR
Arm A of 177Lu-PSMA-617 Comparison
ACTIVE COMPARATORSoC (ADT + ARPI ± docetaxel ± local RT)
Arm P of 177Lu-PSMA-617 Comparison
EXPERIMENTALSoC (ADT + ARPI ± docetaxel ± local RT) + 177Lu-PSMA-617
Interventions
SABR is a way of giving focused high-dose radiotherapy. SABR given with a dose fractionation schedule of 27-30Gy in 3-5 fractions over 1-2 weeks to up to 5 metastatic lesions in the bone and/or non-regional (extra-pelvic) lymph nodes.
177Lu-PSMA-617 is a nuclear medicine therapy. Patients will receive 177Lu-PSMA-617 to a dose of 7.4GBq. Each cycle will consist of 2 doses, 1 week apart (on day 1 and day 8) and will last 6 weeks. Treatment will be given for up to 3 cycles (6 doses).
Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.
Second generation ARPI (Abiraterone Acetate and Prednisolone, Enzalutamide, Apalutamide or Darolutamide). This will be given as standard of care as per local guidelines. Abiraterone acetate will be administered as a single 1000mg once daily dose (4 tablets to be taken together once a day) with prednisolone 5mg once daily to prevent secondary mineralocorticoid excess. Enzalutamide will be administered as a 160mg oral dose (four capsules taken together at the same time every day) with or without food. Enzalutamide is administered daily in 28-day cycles. Apalutamide will be administered as 240mg oral dose (four tablets taken together at the same time every day) with or without food. Apalutamide is administered daily in 28-day cycles. Patients require thyroid function monitoring. Darolutamide will be administered as 600mg oral dose (two 300mg tablets taken together) with or without food. Darolutamide is administered twice daily in 28-day cycles.
Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 44-47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).
Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.
Eligibility Criteria
You may qualify if:
- At least 18 years old.
- Histological confirmation of prostate adenocarcinoma or a strong clinical suspicion of prostate cancer with a plan to confirm the diagnosis formally before any future randomisation.
- Confirmation of metastatic site(s) on CT/MRI and either bone or PET scan. Patients with metastatic disease meeting any of the following criteria are eligible:
- Metastatic disease to the bone (in any distribution).
- Non-regional lymph node metastases of any size or distribution. Lymph nodes that are only visible on PET will not be eligible as sites of metastasis. Note: If lymph nodes are the only site of metastases, then at least one must be at least 1.5cm in short axis AND outside of the pelvis.
- Visceral metastases of any size or distribution.
- Clinical presentation is:
- A. de novo. OR B. relapsed with; (1) continuing hormone sensitivity in the opinion of the investigator, and; (2) all hormone treatments (e.g., ADT and ARPI) will have been completed ≥2 years prior to any future randomisation into any of the comparisons, and; (3) will have received ≤3 years total of ADT at the point of randomisation into any comparison.
- Note: the dates will be checked again at randomisation. It is the responsibility of the investigator to account for the time between registration and randomisation into any comparison.
- Long-term androgen deprivation therapy (ADT) has started or there is an intention to start for a minimum of 2 years.
- WHO Performance Status 0-2 or, if WHO Performance Status 3, deemed to be due to metastatic burden and expected to improve with ADT. Note: Improvement to WHO status 0-2 will be checked again at randomisation into any subsequent comparison.
- Note: For WHO performance status definitions see Appendix 1.
- Willing and able to comply with trial treatments.
- Patient has signed informed consent form for registration into the STAMPEDE2 Trial platform.
You may not qualify if:
- Clinically and pathologically overt small cell carcinoma.
- Metastatic brain disease or leptomeningeal disease.
- Any active malignancies (i.e., progressing or requiring any treatment in the previous 36 months) other than prostate cancer (except non-muscle invasive bladder cancer; nonmelanomatous skin cancer or a malignancy that is considered cured with minimal risk of recurrence).
- Any other medical condition that in the investigator's opinion means the participant is unfit or unsuitable for long-term ADT or the trial treatments in the comparison for which they are being considered.
- Eligibility Criteria For Comparison S Testing SABR:
- Patients who meet the general eligibility criteria can be considered for the SABR comparison. Recruiting sites will assess metastatic disease burden using CT/MRI scans and baseline Tc-99m bone scan or PET scan to assess number of metastatic bone and non-regional lymph node foci, and presence of visceral metastases. Patients will be classified as either 'SABR-eligible' or 'SABR-ineligible' using the following definition.
- Definition of SABR-eligible disease:
- Patients will be classified as SABR-eligible if they meet all the following criteria:
- metastatic lesions (including either bone and/or non-regional lymph node sites).
- Clinician determination that metastatic lesions are considered suitable for SABR on technical grounds (such as proximity of dose limiting normal tissue or tumour volume). Note: Clinical determination can consider next-generation imaging (e.g., PSMA PET-CT or WBMRI) where available. It is the investigator's responsibility to consider the impact of any findings on the suitability of SABR for the patient. Any next-generation imaging used prior to randomisation should be declared at randomisation so that it can be used as a stratification factor.
- Absence of visceral metastases.
- Otherwise, patients will be classified as SABR-ineligible.
- In addition to the general registration eligibility criteria, they need to meet all the following criteria for entry into Comparison S:
- Patient still meets all eligibility criteria for registration in Section 4.4.
- Histological confirmation of prostate adenocarcinoma.
- +41 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- Cancer Research UKcollaborator
- Novartiscollaborator
Study Sites (18)
Mount Vernon Hospital
Barnsley, United Kingdom
Addenbrookes
Cambridge, United Kingdom
Royal Devon University Hospital Trust
Exeter, EX2 5DW, United Kingdom
Royal Devon & Exeter Hospital
Exeter, United Kingdom
The Princess Alexandra Hospital
Harlow, United Kingdom
University College London Hospitals NHS Foundation Trust
London, NW3 2PG, United Kingdom
The Royal Marsden Hospital
London, SW3 6JJ, United Kingdom
Barts Health NHS Trust
London, United Kingdom
North Middlesex Hospital
London, United Kingdom
Royal Free Hospital
London, United Kingdom
The James Cook University Hospital
Middlesbrough, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Derriford Hospital
Plymouth, United Kingdom
Queen Alexandra Hospital
Portsmouth, United Kingdom
Barking, Havering and Redbridge University Hospitals NHS Trust
Romford, United Kingdom
North Tees Health NHS Trust
Stockton-on-Tees, United Kingdom
The Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Kings Mill Hospital
Sutton in Ashfield, United Kingdom
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Louise Brown
MRC CTU at UCL
- PRINCIPAL INVESTIGATOR
Nick James
Institute of Cancer Research, United Kingdom
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 10, 2024
First Posted
March 20, 2024
Study Start
June 11, 2024
Primary Completion (Estimated)
April 1, 2031
Study Completion (Estimated)
March 1, 2032
Last Updated
September 26, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- It will become available for data sharing requests through the MRC CTU process following the primary analysis publication. Research data will be stored a minimum of 25 years.
- Access Criteria
- Data will be available for sharing and researchers wishing to access STAMPEDE2 data should contact the Trial Management Group via the CTU Trial team using the study mailbox in the first instance. A formal data sharing process has been developed at the MRC CTU. Requests for sharing data will need to provide detail on the specific requirements, proposed research, qualifications of researchers and publication plan. The requests will be reviewed by the appropriate STAMPEDE2 committees. A data transfer agreement will be signed prior to the transfer of any information. All patients will be consented for future data sharing and if data requests are approved, only anonymised data will be sent using appropriately encrypted methods for data transfer.
Data will be shared according to the CTU's controlled access approach based on principles outlined in the trial protocol. Requests for sharing data will need to provide detail on the specific requirements, proposed research, qualifications of researchers and publication plan. All non-identifiable data will be available for sharing if approved following the CTU review process. Access to the digital image repository and the stored pathological tissue from researchers outside of the MRC CTU will be obtained through a formal data sharing application detailing the specific requirements, proposed research, investigator qualifications and publication plan. Applications for access to tissue are required separately from access to the shared clinical data.