A Randomised Controlled Platform Trial Testing Treatments in Metastatic Hormone Sensitive Prostate Cancer
- Conditions
- Prostate Cancer Metastatic
- Interventions
- Radiation: Stereotactic Ablative Body Radiotherapy (SABR)Drug: Androgen Deprivation Therapy (ADT)Other: 177Lu-PSMA-617Drug: Androgen Receptor Signalling Inhibitor (ARSI)Radiation: Local Radiotherapy
- Registration Number
- NCT06320067
- Lead Sponsor
- University College, London
- Brief Summary
STAMPEDE2 is a clinical trial comparing three 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.
Comparison N: Arm A(N) versus Arm N (Niraparib-Abiraterone Acetate+Prednisolone (Nira-AA+P)) - Tests whether giving a new drug (Nira-AA+P) slows the spread of the cancer and improves survival. Only people with certain genetic changes in their tumour sample can take part in Comparison N. 682 people will be in this comparison.
Participants may be able to take part in more than one 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 8000
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm S of SABR Comparison Stereotactic Ablative Body Radiotherapy (SABR) SoC (ADT + ARSI ± docetaxel + local RT) + SABR Arm A of 177Lu-PSMA-617 Comparison Local Radiotherapy SoC (ADT + ARSI ± docetaxel ± local RT) Arm A of 177Lu-PSMA-617 Comparison Docetaxel SoC (ADT + ARSI ± docetaxel ± local RT) Arm A of SABR Comparison Androgen Receptor Signalling Inhibitor (ARSI) SoC (ADT + ARSI ± docetaxel + local RT) Arm A of SABR Comparison Androgen Deprivation Therapy (ADT) SoC (ADT + ARSI ± docetaxel + local RT) Arm S of SABR Comparison Local Radiotherapy SoC (ADT + ARSI ± docetaxel + local RT) + SABR Arm A of 177Lu-PSMA-617 Comparison Androgen Receptor Signalling Inhibitor (ARSI) SoC (ADT + ARSI ± docetaxel ± local RT) Arm P of 177Lu-PSMA-617 Comparison 177Lu-PSMA-617 SoC (ADT + ARSI ± docetaxel ± local RT) + 177Lu-PSMA-617 Arm A of 177Lu-PSMA-617 Comparison Androgen Deprivation Therapy (ADT) SoC (ADT + ARSI ± docetaxel ± local RT) Arm P of 177Lu-PSMA-617 Comparison Local Radiotherapy SoC (ADT + ARSI ± docetaxel ± local RT) + 177Lu-PSMA-617 Arm A of SABR Comparison Local Radiotherapy SoC (ADT + ARSI ± docetaxel + local RT) Arm S of SABR Comparison Androgen Deprivation Therapy (ADT) SoC (ADT + ARSI ± docetaxel + local RT) + SABR Arm S of SABR Comparison Androgen Receptor Signalling Inhibitor (ARSI) SoC (ADT + ARSI ± docetaxel + local RT) + SABR Arm N of Niraparib Comparison Niraparib and Abiraterone Acetate Dual Action Tablet DAT SoC (ADT ± docetaxel ± local RT) + Nira-AA+P Arm N of Niraparib Comparison Androgen Deprivation Therapy (ADT) SoC (ADT ± docetaxel ± local RT) + Nira-AA+P Arm P of 177Lu-PSMA-617 Comparison Androgen Deprivation Therapy (ADT) SoC (ADT + ARSI ± docetaxel ± local RT) + 177Lu-PSMA-617 Arm P of 177Lu-PSMA-617 Comparison Androgen Receptor Signalling Inhibitor (ARSI) SoC (ADT + ARSI ± docetaxel ± local RT) + 177Lu-PSMA-617 Arm N of Niraparib Comparison Local Radiotherapy SoC (ADT ± docetaxel ± local RT) + Nira-AA+P Arm A(N) of Niraparib Comparison Androgen Deprivation Therapy (ADT) SoC (ADT + Apalutamide ± docetaxel ± local RT) Arm A(N) of Niraparib Comparison Local Radiotherapy SoC (ADT + Apalutamide ± docetaxel ± local RT) Arm N of Niraparib Comparison Docetaxel SoC (ADT ± docetaxel ± local RT) + Nira-AA+P Arm A of SABR Comparison Docetaxel SoC (ADT + ARSI ± docetaxel + local RT) Arm S of SABR Comparison Docetaxel SoC (ADT + ARSI ± docetaxel + local RT) + SABR Arm P of 177Lu-PSMA-617 Comparison Docetaxel SoC (ADT + ARSI ± docetaxel ± local RT) + 177Lu-PSMA-617 Arm A(N) of Niraparib Comparison Apalutamide SoC (ADT + Apalutamide ± docetaxel ± local RT) Arm A(N) of Niraparib Comparison Docetaxel SoC (ADT + Apalutamide ± docetaxel ± local RT) Arm N of Niraparib Comparison Prednisolone SoC (ADT ± docetaxel ± local RT) + Nira-AA+P Arm N of Niraparib Comparison Abiraterone Acetate SoC (ADT ± docetaxel ± local RT) + Nira-AA+P
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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: 94 months from FPFV, P: 62 months from FPFV and N: 177 months from FPFV. OS is defined as time from randomisation to death from any cause.
Note: Dual-primary outcomes of radiographic Progression-Free-Survival (rPFS) and Overall Survival (OS).
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. Please note that a closed test approach has been used for OS as a dual primary outcome. Continuation of FU for OS will be dependent on observing a significant result for rPFS.Radiographic Progression-Free-Survival (rPFS) Final analysis for each comparison triggered when adequate number of rPFS events have occurred in control arm of each comparison. Anticipate final reporting for rPFS in Comparison S: 58 months from FPFV, P: 42 months from FPFV and N: 65 months from FPFV. rPFS is defined as the time from randomisation to progression of metastatic prostate cancer confirmed by radiographic imaging or death from any cause. The definition for rPFS requires at least one of the following four criteria to be met:
1. Radiological metastatic progression by RECIST v1.1,
2. Progression of bone metastases as defined by PCWG3,
3. Symptomatic skeletal-related events secondary to cancer progression,
4. Death from any cause.
Note: Dual-primary outcomes of radiographic Progression-Free-Survival (rPFS) and Overall Survival (OS).
The final reporting times of rPFS for each comparison below will depend on the recruitment rates and the accuracy of assumed median survival times in the sample size calculations.
- Secondary Outcome Measures
Name Time Method 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. Time from randomisation until the first of:
* Biochemical progression
* Local progression
* Pelvic Lymph node progression
* Distant metastases development or progression
* Skeletal Related Event (where confirmed disease progression)
* Death from prostate cancerProstate 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. Time from randomisation to death from prostate cancer.
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. Compliance with randomised allocation. Formal definitions for compliance with treatment will be pre-specified in the statistical analysis plan. This is still in development. Randomisation until death or end of trial treatment (up to 10 years from randomisation). EQ-5D-5L questionnaire for QoL and cost effectiveness assessment From date of randomisation until death or end of trial, whichever came first (up to 10 years from randomisation). The end of the trial will be determined by the timelines described in the primary outcomes section.
Trial Locations
- Locations (3)
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
The Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
Royal Devon University Hospital Trust
🇬🇧Exeter, United Kingdom