Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE)
Prostate Cancer
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring Stage III Prostate Cancer, Stage IV Prostate Cancer, Recurrent Prostate Cancer, Adenocarcinoma of the prostate
Eligibility Criteria
Inclusion Criteria Participants must fulfil all the criteria in one of the following three categories. Additionally, all patients must fulfil the criteria in Section 4. High-Risk Newly-Diagnosed Non-Metastatic Node-Negative (N0/Nx) Disease Both: • At least two of: T category T3/4, PSA≥40ng/ml or Gleason sum score 8-10 • Intention to treat with radical radiotherapy (unless there is a contra-indication) OR Newly-Diagnosed Metastatic Or Node-Positive Disease At least one of: Stage Tany N+ M0 Stage Tany Nany M+ OR Previously Radically Treated, Now Relapsing (Prior Radical Surgery And/or Radiotherapy) At least one of: • PSA ≥4ng/ml and rising with doubling time less than 6 months • PSA ≥20ng/ml • N+ • M+ AND General Inclusion Criteria Required For All Participants Histologically confirmed prostate adenocarcinoma Intention to treat with long-term androgen deprivation therapy Fit for all protocol treatment and follow up, WHO performance status 0-2 Have completed the appropriate investigations prior to randomisation Adequate haematological function: neutrophil count ≥1.5x109/l and platelets ≥100x109/l Adequate renal function, defined as GFR ≥30ml/min/1.73m2 Written informed consent Willing and expected to comply with follow up schedule Using effective contraceptive method if applicable Medical contraindications to the trial medications are given in Section 6 For WHO performance status definitions see Appendix A 5. General Exclusion Criteria Patients must not fulfil any of the criteria below: Prior systemic therapy for locally-advanced or metastatic prostate cancer (1) (except as listed in the protocol section 4.3) Prior exposure to hormone therapy for a duration of > 12 months, or prior exposure completing < 12 months before randomisation (see section 4.3.1 for permitted prior exposure details) Metastatic brain disease or leptomeningeal disease Abnormal liver functions consisting of any of the following: • Serum bilirubin ≥1.5 x ULN (except for patients with Gilbert's disease, for whom the upper limit of serum bilirubin is 51.3μmol/l or 3mg/dl) • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN - site must indicate at randomisation whether one or both tests are performed at site. Where both results are available both must confirm eligibility. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment Any surgical wound (e.g. TURP) which in the judgement of the responsible clinician may interfere with or be exacerbated by protocol treatment Participant with significant cardiovascular disease, including: • Severe/unstable angina • Myocardial infarction less than 6 months prior to randomisation • Arterial thrombotic events less than 6 months prior to randomisation • Clinically significant cardiac failure requiring treatment, defined as New York Heart Association (NYHA) class II or above (1) • Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 6 months prior to randomisation Any other significant cardiovascular disease that in the investigator's opinion means the participant is unfit for any of the study treatments. Excluding participants receiving docetaxel as part of SOC NYHA classifications can be found in Appendix A 6. Comparison-specific eligibility criteria In addition to the general inclusion and exclusion criteria, the following comparison-specific eligibility criteria apply. For Randomisation to the "Metformin Comparison" Please note from protocol v20 only patients willing to participate in the metabolic sub study should be randomised to the metformin comparison. The sub study will be conducted in a limited number of sites, see section 4.7.4 for further information. In addition to the general inclusion and general exclusion criteria the following comparison-specific inclusion criteria must be met to be eligible for randomisation to the "metformin comparison": • HbA1c <48mmol/mol (equivalent to <6.5%) (1) • Adequate renal function, defined as GFR ≥45ml/min/1.73m (except for Switzerland (2)) • No history of lactic acidosis or pre-disposing conditions Not current or previous treatment with metformin No contra-indications to metformin No current or previous medication for treatment of diabetes Willingness to join the metabolic sub study The method used to determine glomerular filtration rate may vary according to local practice. Equations that either estimate glomerular filtration rate (eGFR) or creatinine clearance (CrCl) may be used and the same threshold value applies. Where possible, HbA1c should be performed prior to commencing SOC docetaxel to reduce the likelihood of corticosteroid-related hyperglycaemia impacting on eligibility. All participants with abnormal baseline HbA1c (i.e. 6.5% or higher) should be informed and referred to their GP for further management. (2) Except Switzerland, please refer to SAKK appendix for local guidance For Randomisation To The "Transdermal Oestradiol Comparison" In addition to the general inclusion and exclusion criteria, participants fulfilling all of the following are eligible for the "transdermal oestradiol comparison": • ≤8 weeks of anti-androgen (AR-antagonists) use • Maximum of 1 dose of monthly or 4-weekly LHRH agonist/antagonist • No prior LHRH agonist injection with a stated duration of effect greater than 1 month • ≤12 weeks since first dose of any hormone therapy • Not had a bilateral orchidectomy • No use of cyproterone acetate (36) prior to randomisation • No known porphyria No known history of deep vein thrombosis or pulmonary embolism confirmed radiologically No known thrombophilic disorder (e.g. Protein C, Protein S, antithrombin deficiency) Not yet started SOC abiraterone, enzalutamide or apalutamide
Sites / Locations
- Kantonsspital Graubuenden
- Lausanne Centre Hospitalier Universitaire
- Winterthur Hospital
- Hirslanden Klinik Aarau
- Universitaetsspital-Basel
- Inselspital Bern
- Liestal Hospital
- Kantonsspital - St. Gallen
- UniversitaetsSpital Zuerich
- City Hospital Triemli
- Berkshire Cancer Centre at Royal Berkshire Hospital
- Royal Bolton Hospital
- Wycombe General Hospital
- Addenbrooke's Hospital
- Broomfield Hospital
- Countess of Chester Hospital
- James Cook University Hospital
- Cumberland Infirmary
- North Devon District Hospital
- Royal Devon and Exeter Hospital
- Royal Bournemouth Hospital
- Dorset County Hospital
- Poole Hospital
- Castle Hill Hospital
- Eastbourne District General Hospital
- Conquest Hospital
- William Harvey Hospital
- Stoke Mandeville Hospital
- Basingstoke and North Hampshire NHS Foundation Trust
- City Hospital (Birmingham)
- Sussex Cancer Centre at Royal Sussex County Hospital
- Burnley General Hospital
- Queen's Hospital
- West Suffolk Hospital
- Mid Cheshire Hospitals Trust- Leighton Hopsital
- Darlington Memorial
- Derbyshire Royal Infirmary
- Doncaster Royal Infirmary
- Russells Hall Hospital
- University Hospital of North Durham
- Gloucestershire Royal Hospital
- Hereford County Hospital
- Kidderminster Hospital
- Leeds Cancer Centre at St. James's University Hospital
- Glenfield Hospital
- Royal Liverpool University Hospital
- University Hospital Aintree
- Helen Rollason Cancer Care Centre at North Middlesex Hospital
- Guy's Hospital
- St. Mary's Hospital
- UCL Cancer Institute
- University College of London Hospitals
- Withington Hospital
- Royal Shrewsbury Hospital
- Stepping Hill Hospital
- Sunderland Royal Hospital
- Torbay Hospital
- Warrington Hospital NHS Trust
- West Cumberland Hospital
- Royal Albert Edward Infirmary
- Worcester Royal Hospital
- Worthing Hospital
- Princess Alexandra Hospital
- Queen's Hospital
- Southend University Hospital NHS Foundation Trust
- South West Wales Cancer Institute At Singleton Hospital
- Cheltenham General Hospital
- St. Bartholomews Hospital
- Queen Elizabeth Hospital - Woolwich
- St. George's Hospital
- Charing Cross Hospital
- Christie Hospital
- Royal Oldham Hospital
- Southampton General Hospital
- Lister Hospital
- Raigmore Hospital
- St. Mary's Hospital
- Airedale General Hospital
- Kent and Canterbury Hospital
- Mid Kent Oncology Centre at Maidstone Hospital
- Queen Elizabeth The Queen Mother Hospital
- Beatson Institute for Cancer Research - Glasgow
- Rosemere Cancer Centre at Royal Preston Hospital
- Southport and Formby District General Hospital
- Mount Vernon Cancer Centre at Mount Vernon Hospital
- Edinburgh Cancer Centre at Western General Hospital
- Freeman Hospital
- Scarborough General Hospital
- Centre for Cancer Research and Cell Biology at Queen's University Belfast
- Nottingham City Hospital
- King's Mill Hospital
- Churchill Hospital
- Queen Alexandra Hospital
- Ayr Hospital
- Royal United Hospital
- Bristol Haematology and Oncology Centre
- Musgrove Park Hospital
- Weston General Hospital
- Yeovil District Hospital
- Cancer Research Centre at Weston Park Hospital
- Royal Stoke University Hospital
- Ipswich Hospital
- St. Luke's Cancer Centre at Royal Surrey County Hospital
- Royal Marsden - Sutton
- Northern Centre for Cancer Treatment at Newcastle General Hospital
- South Tyneside District Hospital
- Bronglais General Hospital
- Velindre Cancer Center at Velindre Hospital
- Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
- Good Hope Hospital
- Bradford Royal Infirmary
- Huddersfield Royal Infirmary
- Great Western Hospital
- Clatterbridge Centre for Oncology
- Barnet General Hospital
- Colchester General Hospital
- Forth Valley Hospital
- Lincoln Hospital
- North Tees Hospital
- New Cross Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Active Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm A: Standard of Care
Arm B: Zoledronic Acid
Arm C: Docetaxel
Arm D: Celecoxib
Arm E: Zoledronic Acid & Docetaxel
Arm F: Zoledronic Acid & Celecoxib
Arm G: Abiraterone
Arm H: M1 RT
Arm J: Abiraterone * Enzalutamide
Arm K: Metformin
Arm L: tE2
Androgen Deprivation Therapy [ADT] (plus Radiotherapy for newly-diagnosed non-metastatic disease, plus or minus Docetaxel, plus or minus Abiraterone)[Control]
(ADT + zoledronic acid) NO LONGER RECRUITING
(ADT + docetaxel + prednisolone) NO LONGER RECRUITING
(ADT + celecoxib) NO LONGER RECRUITING
(ADT + zoledronic acid + docetaxel + prednisolone) NO LONGER RECRUITING
(ADT + zoledronic acid + celecoxib) NO LONGER RECRUITING
(ADT + abiraterone acetate + prednisolone) NO LONGER RECRUITING
(ADT + radiotherapy to the prostate) NO LONGER RECRUITING
(ADT + abiraterone + enzalutamide + Prednisolone) NO LONGER RECRUITING
(ADT + Metformin) RECRUITING IN SELECTED SITES
(Transdermal oestradiol) RECRUITING