STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial


Condition: Prostate Cancer

Intervention:

  • Drug: Celecoxib
  • Drug: Docetaxel
  • Drug: Prednisolone
  • Drug: ADT
  • Drug: Zoledronic Acid
  • Drug: Abiraterone
  • Radiation: Radiotherapy to the prostate
  • Drug: Enzalutamide
  • Drug: Metformin
  • Drug: Transdermal Oestradiol

Purpose: The overall aim of this trial, which is called STAMPEDE, is to assess novel approaches for the treatment of men with prostate cancer who are starting long-term ADT for the first time, termed hormone-naïve prostate cancer. This trial aims to see if we can improve the way in which prostate cancer is currently managed, either by adding new treatments to the standard approach or by modifying the type of hormone therapy aiming to improve quality-of-life by reducing the side effects of treatment. Each new treatment approach is compared against a control arm receiving the current standard treatments. We aim to identify treatment strategies that enable men to live longer, or as long but with an improved quality-of-life, as well as offering value for money for the health service. Since opening to accrual in Oct-2005, the trial has tested many ways of treating prostate cancer and some results are now already known. More than 10,000 men will join the trial with answers becoming available throughout the trial. New patients joining the trial from Protocol version 17.0 onwards (activated in December 2018) may be eligible to join one of two treatment comparisons, metformin (treatment group K; the "metformin comparison") and transdermal oestradiol (treatment group L; the "transdermal oestradiol comparison"). A computer program will be used to allocate which treatment each participant receives, using a chance process. Summary of the research arms in STAMPEDE trial platform Summary of research treatment groups currently open to recruitment (June 2017) 1. Metformin (Arm K): This anti-diabetic medication is proposed to have both anti-cancer effects and may help prevent the adverse metabolic effects of long-term ADT. STAMPEDE will investigate whether adding metformin to the current standard-of-care for non-diabetic men can improve all-cause survival. 2. Transdermal oestradiol (Arm L): This is an alternative form of hormone treatment which has been shown to suppress testosterone as effectively as standard ADT and avoid some of the side-effects. It may also help to avoid the adverse metabolic effects and fatigue and therefore improve overall quality of life compared with standard forms of ADT. STAMPEDE will investigate whether transdermal oestradiol can treat the cancer as well as current standard forms of ADT. 3. Control group (Arm A): Patients allocated to this group receive the current standard-of-care ADT +/- RT +/- docetaxel.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT00268476

Sponsor: Medical Research Council

Primary Outcome Measures:

  • Measure: Overall survival
  • Time Frame: 1:Not applicable
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Failure-free survival
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Cost effectiveness by EuroQol
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Number of participants with treatment-related side effects as assessed by CTCAE v4.0
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Skeletal related events
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Biochemical failure
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Progression-free survival
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Lymph node progression
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Distant metastases
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Treatment for progression
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Disease-specific survival
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Non-prostate cancer death
  • Time Frame: 1:Not applicable
  • Safety Issue:
  • Measure: Metabolic effects
  • Time Frame: 1:Not applicable
  • Safety Issue:

Estimated Enrollment: 12200

Study Start Date: July 8, 2005

Phase: Phase 2/Phase 3

Eligibility:

  • Age: minimum N/A maximum 120 Years
  • Gender: Male

Inclusion Criteria:

  • Participants must fulfil both of the criteria in Section 1 or at least one criterion in Section 2 or at least one criterion in Section 3 of the protocol. Additionally, all patients must fulfil the criteria in Section 4. 1. High-Risk Newly-Diagnosed Non-Metastatic Node-Negative 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; exemption can be sought in advance of consent, after discussion with CTU) OR 2. Newly-Diagnosed Metastatic Or Node-Positive Disease At least one of:
  • Stage Tany N+ M0
  • Stage Tany Nany M+ OR 3. 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 4. For All Patients 1. Histologically confirmed prostate adenocarcinoma 2. Intention to treat with long-term androgen deprivation therapy 3. Treating clinician and patient should have decided if docetaxel is to be part of the standard-of-care prior to randomisation 4. Fit for all protocol treatment1 and follow-up, WHO performance status 0-22 5. Have completed the appropriate investigations prior to randomisation 6. Adequate haematological function: neutrophil count >1.5x109/l and platelets >100x109/l 7. Adequate renal function, defined as GFR >30ml/min/1.73m2 8. Written informed consent 9. Willing and expected to comply with follow-up schedule 10. Using effective contraceptive method if applicable 1. Medical contraindications to the trial medications are given in Section 6 2. For WHO performance status definitions see Appendix A Exclusion Criteria Patients must not fulfil any of the criteria, below. 1. Prior systemic therapy for locally-advanced or metastatic prostate cancer except as listed above 2. Metastatic brain disease or leptomeningeal disease 3. 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 4. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment 5. Any surgery (e.g. TURP) performed within the past 4 weeks 6. 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 above1
  • Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 6 months prior to randomisation
  • Or any other significant cardiovascular disease that in the investigator's opinion means the participant is unfit for any of the study treatments. 7. Prior chemotherapy for prostate cancer2 8. Prior exposure to long-term hormone therapy before randomisation 9. Prior exposure to systemic treatment for prostate cancer (excluding ADT or participants receiving abiraterone as part of SOC) 1. NYHA classifications can be found in Appendix A 2. Excluding participants receiving docetaxel as part of SOC For Randomisation to the "Metformin Comparison" 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%)* •Adequate renal function, defined as GFR ≥45ml/min/1.73m2 •No history of lactic acidosis or pre-disposing conditions •Not current or previous treatment with metformin •No contra-indications to metformin 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. For Randomisation To The "Transdermal Oestradiol Comparison" In addition to the general inclusion and

Exclusion Criteria:

  • Patients must not fulfil any of the criteria, below. 1. Prior systemic therapy for locally-advanced or metastatic prostate cancer except as listed above 2. Metastatic brain disease or leptomeningeal disease 3. 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 4. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment 5. Any surgery (e.g. TURP) performed within the past 4 weeks 6. 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 above1
  • Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 6 months prior to randomisation
  • Or any other significant cardiovascular disease that in the investigator's opinion means the participant is unfit for any of the study treatments. 7. Prior chemotherapy for prostate cancer2 8. Prior exposure to long-term hormone therapy before randomisation 9. Prior exposure to systemic treatment for prostate cancer (excluding ADT or participants receiving abiraterone as part of SOC) 1. NYHA classifications can be found in Appendix A 2. Excluding participants receiving docetaxel as part of SOC For Randomisation to the "Metformin Comparison" 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%)* •Adequate renal function, defined as GFR ≥45ml/min/1.73m2 •No history of lactic acidosis or pre-disposing conditions •Not current or previous treatment with metformin •No contra-indications to metformin 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. 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 •≤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 (77) 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 planned to receive SOC abiraterone

Contact:

  • STAMPEDE Trial Team
  • +44 (0)20 7670 4700

Locations:

  • Kantonsspital Graubuenden
  • Chur Graubunden CH-7000 Switzerland
  • Lausanne Centre Hospitalier Universitaire
  • Lausanne Vaud CH-1011 Switzerland
  • Winterthur Hospital
  • Winterthur Zurich CH-8401 Switzerland
  • Hirslanden Klinik Aarau
  • Aarau CH-5000 Switzerland
  • Universitaetsspital-Basel
  • Basel CH-4031 Switzerland
  • Inselspital Bern
  • Berne CH-3010 Be Switzerland
  • Liestal Hospital
  • Liestal CH-4410 Switzerland
  • Kantonsspital - St. Gallen
  • St. Gallen CH-9007 Switzerland
  • UniversitaetsSpital Zuerich
  • Zurich CH-8091 Switzerland
  • City Hospital Triemli
  • Zurich Switzerland
  • Berkshire Cancer Centre at Royal Berkshire Hospital
  • Reading Berkshire RG1 5AN United Kingdom
  • Royal Bolton Hospital
  • Farnworth Bolton BL4 0JR United Kingdom
  • Wycombe General Hospital
  • High Wycombe Buckinghamshire HP11 2TT United Kingdom
  • Addenbrooke's Hospital
  • Cambridge Cambridgeshire CB2 0QQ United Kingdom
  • Broomfield Hospital
  • Broomfield Chelmsford CM1 7ET United Kingdom
  • Countess of Chester Hospital
  • Chester Chesire CH2 1UL United Kingdom
  • James Cook University Hospital
  • Middlesbrough County Durham TS4 3BW United Kingdom
  • Cumberland Infirmary
  • Carlisle Cumbria CA2 7HY United Kingdom
  • North Devon District Hospital
  • Barnstaple Devon EX31 4JB United Kingdom
  • Royal Devon and Exeter Hospital
  • Exeter Devon EX2 5DW United Kingdom
  • Royal Bournemouth Hospital
  • Bournemouth Dorset BH7 7DW United Kingdom
  • Dorset County Hospital
  • Dorchester Dorset DT1 2JY United Kingdom
  • Poole Hospital
  • Poole Dorset BH15 2JB United Kingdom
  • Castle Hill Hospital
  • Cottingham East Riding Of Yorkshire HU16 5JQ United Kingdom
  • Eastbourne District General Hospital
  • Eastbourne East Sussex BN21 2UD United Kingdom
  • Conquest Hospital
  • Saint Leonards-on-Sea East Sussex TN37 7PT United Kingdom
  • William Harvey Hospital
  • Ashford England TN24 0LZ United Kingdom
  • Stoke Mandeville Hospital
  • Aylesbury England HP21 8AL United Kingdom
  • Basingstoke and North Hampshire NHS Foundation Trust
  • Basingstoke England RG24 9NA United Kingdom
  • City Hospital (Birmingham)
  • Birmingham England B18 7QH United Kingdom
  • Sussex Cancer Centre at Royal Sussex County Hospital
  • Brighton England BN2 5BE United Kingdom
  • Burnley General Hospital
  • Burnley England BB10 2PQ United Kingdom
  • Queen's Hospital
  • Burton-upon-Trent England DE13 0RB United Kingdom
  • West Suffolk Hospital
  • Bury St. Edmunds England IP33 2QZ United Kingdom
  • Mid Cheshire Hospitals Trust- Leighton Hopsital
  • Crewe England CW1 4QJ United Kingdom
  • Darlington Memorial
  • Darlington England DL3 6HX United Kingdom
  • Derbyshire Royal Infirmary
  • Derby England DE22 3NE United Kingdom
  • Doncaster Royal Infirmary
  • Doncaster England DN2 5LT United Kingdom
  • Russells Hall Hospital
  • Dudley England DY1 2HQ United Kingdom
  • University Hospital of North Durham
  • Durham England DH1 5TW United Kingdom
  • Gloucestershire Royal Hospital
  • Gloucester England GL1 3NN United Kingdom
  • Hereford County Hospital
  • Hereford England HR1 2ER United Kingdom
  • Kidderminster Hospital
  • Kidderminster England DY11 6RJ United Kingdom
  • Leeds Cancer Centre at St. James's University Hospital
  • Leeds England LS9 7TF United Kingdom
  • Glenfield Hospital
  • Leicester England United Kingdom
  • Royal Liverpool University Hospital
  • Liverpool England L7 8XP United Kingdom
  • University Hospital Aintree
  • Liverpool England L9 7AL United Kingdom
  • Helen Rollason Cancer Care Centre at North Middlesex Hospital
  • London England N18 1QX United Kingdom
  • Guy's Hospital
  • London England SE1 9RT United Kingdom
  • St. Mary's Hospital
  • London England W2 1NY United Kingdom
  • UCL Cancer Institute
  • London England WC1E 6DD United Kingdom
  • University College of London Hospitals
  • London England WIT 3AA United Kingdom
  • Withington Hospital
  • Manchester England M20 8LR United Kingdom
  • Royal Shrewsbury Hospital
  • Shrewsbury England SY3 8XQ United Kingdom
  • Stepping Hill Hospital
  • Stockport England SK2 7JE United Kingdom
  • Sunderland Royal Hospital
  • Sunderland England SR4 7TP United Kingdom
  • Torbay Hospital
  • Torquay England TQ2 7AA United Kingdom
  • Warrington Hospital NHS Trust
  • Warrington England WA5 1QG United Kingdom
  • West Cumberland Hospital
  • Whitehaven England CA28 8JG United Kingdom
  • Royal Albert Edward Infirmary
  • Wigan England WN1 2NN United Kingdom
  • Worcester Royal Hospital
  • Worcester England WR5 1DD United Kingdom
  • Worthing Hospital
  • Worthing England BN11 2DH United Kingdom
  • Princess Alexandra Hospital
  • Harlow Essex CM20 1QX United Kingdom
  • Queen's Hospital
  • Romford Essex RM7 0AG United Kingdom
  • Southend University Hospital NHS Foundation Trust
  • Westcliff-On-Sea Essex SS0 0RY United Kingdom
  • South West Wales Cancer Institute At Singleton Hospital
  • Swansea Glamorgan SA2 8QA United Kingdom
  • Cheltenham General Hospital
  • Cheltenham Gloucestershire GL53 7AN United Kingdom
  • St. Bartholomews Hospital
  • London Greater London EC1A 7BE United Kingdom
  • Queen Elizabeth Hospital - Woolwich
  • London Greater London SE18 4QH United Kingdom
  • St. George's Hospital
  • London Greater London SW17 0QT United Kingdom
  • Charing Cross Hospital
  • London Greater London W6 8RF United Kingdom
  • Christie Hospital
  • Manchester Greater Manchester M20 4BX United Kingdom
  • Royal Oldham Hospital
  • Oldham Greater Manchester OL1 2JH United Kingdom
  • Southampton General Hospital
  • Southampton Hampshire S016 6YD United Kingdom
  • Lister Hospital
  • Stevenage Hertfordshire SG1 4AB United Kingdom
  • Raigmore Hospital
  • Inverness Highland IV2 3UJ United Kingdom
  • St. Mary's Hospital
  • Newport Isle Of Wight PO30 5TG United Kingdom
  • Airedale General Hospital
  • Steeton Keighley BD20 6TD United Kingdom
  • Kent and Canterbury Hospital
  • Canterbury Kent CT1 3NG United Kingdom
  • Mid Kent Oncology Centre at Maidstone Hospital
  • Maidstone Kent ME16 9QQ United Kingdom
  • Queen Elizabeth The Queen Mother Hospital
  • Margate Kent CT9 4AN United Kingdom
  • Beatson Institute for Cancer Research - Glasgow
  • Glasgow Lanarkshire G12 0YN United Kingdom
  • Rosemere Cancer Centre at Royal Preston Hospital
  • Preston Lancashire PR2 4QF United Kingdom
  • Southport and Formby District General Hospital
  • Southport Merseyside PR8 6PN United Kingdom
  • Mount Vernon Cancer Centre at Mount Vernon Hospital
  • Northwood Middlesex HA6 2RN United Kingdom
  • Edinburgh Cancer Centre at Western General Hospital
  • Edinburgh Midlothian EH4 2XU United Kingdom
  • Freeman Hospital
  • Newcastle Newcastle-upon-Tyne NE7 7DN United Kingdom
  • Scarborough General Hospital
  • Scarborough North Yorkshire YO12 6QL United Kingdom
  • Centre for Cancer Research and Cell Biology at Queen's University Belfast
  • Belfast Northern Ireland BT9 7AB United Kingdom
  • Nottingham City Hospital
  • Nottingham Nottinghamshire NG5 1PB United Kingdom
  • King's Mill Hospital
  • Sutton-in-Ashfield Nottinghamshire NG17 4JL United Kingdom
  • Churchill Hospital
  • Oxford Oxfordshire OX3 7LE United Kingdom
  • Queen Alexandra Hospital
  • Cosham Portsmouth P06 3LY United Kingdom
  • Ayr Hospital
  • Ayr Scotland KA6 6DX United Kingdom
  • Royal United Hospital
  • Bath Somerset BA1 3NG United Kingdom
  • Bristol Haematology and Oncology Centre
  • Bristol Somerset BS2 8ED United Kingdom
  • Musgrove Park Hospital
  • Taunton Somerset TA1 5DA United Kingdom
  • Weston General Hospital
  • Weston Super Mare Somerset BS23 4TQ United Kingdom
  • Yeovil District Hospital
  • Yeovil Somerset BA21 4AT United Kingdom
  • Cancer Research Centre at Weston Park Hospital
  • Sheffield South Yorkshire S10 2SJ United Kingdom
  • Royal Stoke University Hospital
  • Stoke-on-Trent Staffordshire ST4 6QG United Kingdom
  • Ipswich Hospital
  • Ipswich Suffolk IP4 5PD United Kingdom
  • St. Luke's Cancer Centre at Royal Surrey County Hospital
  • Guildford Surrey GU2 7XX United Kingdom
  • Royal Marsden - Sutton
  • Sutton Surrey SM2 5PT United Kingdom
  • Northern Centre for Cancer Treatment at Newcastle General Hospital
  • Newcastle-Upon-Tyne Tyne & Wear NE4 6BE United Kingdom
  • South Tyneside District Hospital
  • South Shields Tyne & Wear NE34 0PL United Kingdom
  • Bronglais General Hospital
  • Aberystwyth Wales SY23 1ER United Kingdom
  • Velindre Cancer Center at Velindre Hospital
  • Cardiff Wales CF14 2TL United Kingdom
  • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
  • Birmingham West Midlands B15 2TH United Kingdom
  • Good Hope Hospital
  • Sutton Coldfield West Midlands B75 7RR United Kingdom
  • Bradford Royal Infirmary
  • Bradford West Yorkshire BD9 6RJ United Kingdom
  • Huddersfield Royal Infirmary
  • Huddersfield West Yorkshire HD3 3EA United Kingdom
  • Great Western Hospital
  • Swindon Wiltshire SN3 6BB United Kingdom
  • Clatterbridge Centre for Oncology
  • Bebington Wirral CH63 4JY United Kingdom
  • Barnet General Hospital
  • Barnet EN5 3DJ United Kingdom
  • Colchester General Hospital
  • Colchester CO4 5JL United Kingdom
  • Forth Valley Hospital
  • Larbert FK5 4WR United Kingdom
  • Lincoln Hospital
  • Lincoln LN2 5QY United Kingdom
  • North Tees Hospital
  • Stockton-on-Tees TS19 8PE United Kingdom
  • New Cross Hospital
  • Wolverhampton WV10 0QP United Kingdom

View trial on ClinicalTrials.gov


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