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.
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.
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.
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.
Parallel
Stereotactic Ablative Body Radiotherapy (SABR)
RadiationSABR 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
Other intervention177Lu-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).
Androgen Deprivation Therapy (ADT)
DrugLong-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.
Androgen Receptor Signalling Inhibitor (ARPI)
DrugSecond 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.
Radiotherapy to Prostate ± Pelvic Nodes
RadiationEither 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).
Docetaxel
DrugMaximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.
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.
Failure-Free Survival (FFS)
Time from randomisation until the first of: * Biochemical progression * Clinical progression such as symptomatic local progression leading to intervention * Radiographic confirmed progression including local progression, pelvic lymph node progression, progression of an existing metastatic site or development of new metastatic site defined as lymph nodes outside the pelvis, bone or organ involvement * Symptomatic skeletal-related events secondary to cancer progression * Death from any cause
Radiographic Progression-Free-Survival (rPFS)
Time from randomisation until the first of: * Radiographic confirmed progression of an existing metastatic site or development of a new metastatic site defined as lymph nodes outside the pelvis, bone or organ involvement * Symptomatic skeletal-related events secondary to cancer progression * Death from any cause
Prostate cancer specific survival (PCSS)
Time from randomisation to death from prostate cancer.
Safety through reporting of SAEs
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