Prostate Cancer Metastatic
Conditions
Keywords
Hormone sensitive metastatic prostate cancer, Stereotactic ablative body radiotherapy (SABR), PSMA-Lutetium
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.
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.
OTHER177Lu-PSMA-617
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).
DRUGAndrogen Deprivation Therapy (ADT)
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.
DRUGAndrogen Receptor Signalling Inhibitor (ARPI)
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.
RADIATIONRadiotherapy to Prostate ± Pelvic Nodes
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).
DRUGDocetaxel
Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.
Sponsors
Cancer Research UK
Novartis
University College, London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Platform trial testing two research comparisons where patients are randomised either to experimental treatments in Arms S and P or their corresponding SoC control Arms A(S) and A(P).
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Registration 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. Registration
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; nonmelanomatous 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. 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: 1. Patient still meets all eligibility criteria for registration in Section 4.4. 2. Histological confirmation of prostate adenocarcinoma. 3. Newly diagnosed (de novo) metastatic disease that is considered eligible for SABR according to the above definition. 4. Patient has started ADT and randomisation is ≤12 weeks since the start of ADT. 5. WHO performance status 0-2 (see Appendix 1). 6. Patient has provided signed informed consent for participation in Comparison S.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: ~84 months (7 years) from FPFV, P: ~64 months (5.3 years) from FPFV. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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) | 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 | — |
| 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 * 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 |
| 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). | — |
| Resource use for cost-effectiveness assessment | 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. | — |
| 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. | — |
Countries
United Kingdom
Contacts
Primary ContactPamela Niem
Backup ContactAaron Horsey
Outcome results
None listed