Metastatic hormone-sensitive prostate cancer Cancer
Conditions
Interventions
Current interventions as of 11/08/2025:
STAMPEDE2 is a platform trial testing the addition of experimental treatments to Standard of Care (SoC) for metastatic hormone-sensitive prostate cancer (mHSPC)
Sponsors
University College London
Eligibility
Sex/Gender
Male
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 11/08/2025: General Inclusion Criteria: 1. At least 18 years old. 2. 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. 3. 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. 4. 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. 5. Long-term androgen deprivation therapy (ADT) has started or there is an intention to start for a minimum of 2 years. 6. 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. 7. Willing and able to comply with trial treatments. 8. Patient has signed informed consent form for registration into the STAMPEDE2 Trial platform. 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 the 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: • 1-5 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: 1. Patient still meets all eligibility crite
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 11/08/2025: General Exclusion Criteria: 1. Clinically and pathologically overt small cell carcinoma. 2. Metastatic brain disease or leptomeningeal disease. 3. 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; non-melanomatous skin cancer or a malignancy that is considered cured with minimal risk of recurrence). 4. 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. Exclusion Criteria For Comparison S Testing SABR: 1. Patient has relapsed prostate cancer. 2. Prior radical treatment to the prostate (e.g., radical surgery and/or radiotherapy). 3. Intracranial metastatic disease. 4. Prior treatment to a metastatic site (e.g., radiotherapy, surgery or RFA). 5. Significant or progressive neurological deficit such that emergency (within 24 hours) surgery or radiation required (e.g., metastatic spinal cord compression, or impingement of the cord or any other clinical scenario whereby urgent radiotherapy to the spine is required). 6. Any condition or co-morbidities that, in the judgement of the clinician, preclude procedures required to facilitate radiotherapy delivery, e.g.: a. Disease staging and follow-up. b. Radiotherapy planning procedures. 7. Any condition or co-morbidities that, in the judgement of the clinician, preclude the safe delivery of radiotherapy to the prostate (± pelvic lymph nodes) and/or metastases, e.g., inflammatory bowel disease, significant systemic connective tissue disorder, radiological evidence of idiopathic pulmonary fibrosis). 8. Active malignancy other than prostate cancer within the last 36 months. Exclusion Criteria For Comparison P Testing 177Lu-PSMA-617: 1. Prior treatment with any of the following: a. Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 b. PSMA-targeted radioligand therapy 2. Symptomatic cord compression, or clinical/radiological findings indicative of impending cord compression. 3. Any condition that precludes raised arms position. 4. Unmanageable bladder outflow obstruction or urinary incontinence. Note: bladder outflow obstruction or urinary incontinence which is manageable and controlled with best available standard of care (incl. drainage, pads) is permitted. 5. Imaging Sub-study only: Contraindication to MRI (e.g., pacemakers, except MRI-compatible pacemakers). Previous exclusion criteria: General exclusion criteria 1. Clinically and pathologically overt small cell carcinoma 2. Metastatic brain disease or leptomeningeal disease 3. 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; non-melanomatous skin cancer or a malignancy that is considered cured with minimal risk of recurrence) 4. Any other medical condition that in the investigator's opinion means the participant is unfit or unsuitable for long-term ARSI or the trial treatments in the comparison for which they are being considered. Exclusion criteria For comparison S testing SABR 1. Prior radical treatment to the prostate (e.g., radical surgery and/or radiotherapy). 2. Intracranial metastatic disease 3. Prior treatment to a metastatic site (e.g., radiotherapy, surgery or RFA) 4. Significant or progressi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Corrected 06/02/2026: Current primary outcome measure as of 11/08/2025: For both Comparisons S and P, the primary outcome is Overall Survival (OS) defined as time from randomisation to death from any cause. 2.1. Comparison S: 2.1.2. OS data maturity requires that 289 deaths have occurred in the control arm and this is expected to occur 79 months (6.6 years) after First Patient First Visit (FPFV). 2.2. Comparison P: 2.2.2. OS data maturity requires that 286 deaths have occurred in the control arm and this is expected to occur 59 months (5 years) from First Patient First Visit (FPFV). If necessary, NHS Registry data will be used for events beyond trial closure. Previous primary outcome measure: All three comparisons will use dual-primary outcome measures of: 1. Radiological progression-free survival (rPFS), defined as the time from randomisation to metastatic cancer progression or death from any cause. The definition for rPFS requires at least one of the following four criteria to be met: 1.1. Progression of bone metastases as defined by PCWG3 1.2. Radiological metastatic progression by RECIST v1.1 1.3. Symptomatic skeletal-related events secondary to cancer progression 1.4. Death from any cause. 2. Overall survival (OS), defined as the time from randomisation to death from any cause. 2.1. Comparison S: 2.1.1. rPFS is expected to report when 231 rPFS events have occurred in the control arm ~4.8 years from FPFV 2.1.2. OS is expected to report after 341 deaths have occurred in the control arm ~7.8 years from FPFV 2.2. Comparison P: 2.2.1. rPFS is expected to report when 228 rPFS events have occurred in the control arm ~3.5 years from FPFV 2.2.2. OS is expected to report after 337 deaths have occurred in the control arm ~5.2 years from FPFV 2.3. Comparison N: 2.3.1. rPFS is expected to report when 86 rPFS events have occurred in the control arm ~5.4 years from FPFV 2.3.2. OS is expected to report when 210 deaths have occurred in the control arm ~14.8 years from FPFV | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 11/08/2025: Analyses will also be undertaken for the following secondary outcomes: 1. Failure-free survival (FFS) reported alongside the primary outcome measures when those are mature enough for reporting 2. Radiographic Progression-Free-Survival (rPFS) 3. Prostate cancer-specific survival (PCSS) reported alongside the primary outcome measures when those are mature for reporting 4. Safety through reporting of SAEs reported as part of annual DSUR reports and in any publications for the primary and secondary outcomes 5. Toxicity using CTCAE classification data will be reviewed as part of closed IDMC meetings throughout the trial. Results for these outcomes will be reported alongside the primary outcome measures when those are mature for reporting 6. Compliance with randomised allocation data will be reviewed as part of closed IDMC meetings throughout the trial. Results for these outcomes will be reported alongside the primary outcome measures when those are mature for reporting. 7. Resource use for cost-effectiveness assessment 8. EQ-5D-5L questionnaire for cost-effectiveness assessment will be collected at baseline, 3 months and then 6-monthly until death or end of the trial. Reporting of these results will be specific to each comparison and likely to coincide with the reporting of the primary outcomes Additional more detailed FACT-RNT Quality of life (QoL) questionnaires will be collected in patients taking part in the Imaging sub-study. Patient Reported Outcome Measures (PROMS) have not been included in this first version of the protocol but will be added later as a substantial amendment. Previous secondary outcome measures: Analyses will also be undertaken for the following secondary outcomes: 1. Failure-free survival (FFS) reported alongside the primary outcome measures when those are mature enough for reporting 2. Prostate cancer-specific survival (PCSS) reported alongside the primary outcome measures when those are mat | — |
Countries
England, United Kingdom
Contacts
Public ContactStudy Team
Outcome results
None listed