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).
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.
⁃ 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.
• Registration Exclusion Criteria:
⁃ 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:
• 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:
⁃ Patient still meets all eligibility criteria for registration in Section 4.4.
⁃ Histological confirmation of prostate adenocarcinoma.
⁃ Newly diagnosed (de novo) metastatic disease that is considered eligible for SABR according to the above definition.
⁃ Patient has started ADT and randomisation is ≤12 weeks since the start of ADT.
⁃ WHO performance status 0-2 (see Appendix 1).
⁃ Patient has provided signed informed consent for participation in Comparison S.