Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE)

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

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 Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Zoledronic Acid; Drug: Metformin; Drug: Celecoxib; Drug: Prednisolone; Drug: Enzalutamide; Drug: ADT; Drug: Abiraterone; Radiation: Radiotherapy to the prostate; Drug: Transdermal Oestradiol

Detailed Description

STAMPEDE (also known as MRC PR08) is a multi-arm multi-stage (MAMS) randomised controlled trial recruiting in the UK and Switzerland. It aims to evaluate multiple therapeutic strategies in the management of high-risk locally advanced and metastatic hormone-naïve prostate cancer. Each novel treatment strategy is compared against a single, contemporaneous control arm. When the trial originally opened in 2005 there were 6 research arms enabling 5 randomised comparisons. Each comparison is evaluated in stages with pre-planned interim analyses after which recruitment may be halted should the experimental treatment fail to reach a "hurdle" of activity. Patient data from all arms and all stages are, however, included in the final analyses of the primary outcome measure, even if the investigational arm did not proceed to the final stage.

Providing sufficient activity is demonstrated, recruitment continues to the final stage and then an assessment of efficacy is determined based on the primary outcome of overall survival. Patient data from all arms and all stages are included in the final analyses of the primary outcome measure, even if the investigational arm did not proceed to the final stage.

The original comparisons which have all now been reported, evaluated a bisphosphonate (zoledronic acid), a cytotoxic chemotherapeutic agent (docetaxel) and a cyclooxygenase (Cox 2) inhibitor (celecoxib), as single agents or combinations. Since the start of the trial, a number of new research arms have been added to STAMPEDE over time to evaluate: abiraterone, a steroid synthesis inhibitor; prostate radiotherapy for patients with newly diagnosed metastatic disease; enzalutamide, an inhibitor of androgen receptor signalling, given with abiraterone; and metformin, an anti-diabetic medication and transdermal oestradiol, to be given as an alternative form of ADT.

Objectives:

Primary

To compare the safety and efficacy of novel therapeutic strategies against the current standard-of-care for men with high-risk locally advanced or metastatic prostate cancer starting long-term ADT for the first time.

Outline: This is a randomised, controlled, multi-centre MAMS trial platform. Patients are current randomised to 1 of 3 arms: control group (arm A), metformin treatment group (arm K) and transdermal oestradiol (Arm L). The other arms are all closed to recruitment with results known for all the original comparisons and awaited for others added since the trial commenced.

Patient population: STAMPEDE recruits both men with high-risk locally advanced prostate cancer and men with metastatic prostate cancer, all of whom must be starting long-term ADT for the first time. Patients who received previous radical treatment and are now relapsing with high-risk features are also eligible.

Follow-up: All patients are follow-up life long

Sub-studies: There are several translational sub-studies ongoing as part of STAMPEDE. Participation is optional. These currently include several translational sub-studies involving sample collection: saliva collection for germline DNA analysis, sequential circulating tumour DNA analysis and FFPE tumour block retrieval for DNA and RNA analysis. Other sub-studies include a QOL sub-study and an imaging sub-study.

• Study Type: Interventional
• Enrollment (Actual): 11992
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 116 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

1. 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

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. General Inclusion Criteria Required For All Participants

1. Histologically confirmed prostate adenocarcinoma
2. Intention to treat with long-term androgen deprivation therapy
3. Fit for all protocol treatment and follow up, WHO performance status 0-2
4. Have completed the appropriate investigations prior to randomisation
5. Adequate haematological function: neutrophil count ≥1.5x109/l and platelets ≥100x109/l
6. Adequate renal function, defined as GFR ≥30ml/min/1.73m2
7. Written informed consent
8. Willing and expected to comply with follow up schedule
9. 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

5. General Exclusion Criteria

Patients must not fulfil any of the criteria below:

1. Prior systemic therapy for locally-advanced or metastatic prostate cancer (1) (except as listed in the protocol section 4.3)
2. 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)
3. Metastatic brain disease or leptomeningeal disease

4. 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.

5. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment
6. Any surgical wound (e.g. TURP) which in the judgement of the responsible clinician may interfere with or be exacerbated by protocol treatment

7. 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.

     1. Excluding participants receiving docetaxel as part of SOC
     2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Standard of Care; Androgen Deprivation Therapy [ADT] (plus Radiotherapy for newly-diagnosed non-metastatic disease, plus or minus Docetaxel, plus or minus Abiraterone)[Control]	Drug: ADT; Other Names: Androgen Deprivation Therapy
Experimental: Arm B: Zoledronic Acid; (ADT + zoledronic acid) NO LONGER RECRUITING	Drug: Zoledronic Acid; Other Names: Zometa; Drug: ADT; Other Names: Androgen Deprivation Therapy
Experimental: Arm C: Docetaxel; (ADT + docetaxel + prednisolone) NO LONGER RECRUITING	Drug: Docetaxel; Other Names: Taxotere; Drug: Prednisolone; Other Names: Prednisone; Drug: ADT; Other Names: Androgen Deprivation Therapy
Experimental: Arm D: Celecoxib; (ADT + celecoxib) NO LONGER RECRUITING	Drug: Celecoxib; Other Names: Celebrex; Drug: ADT; Other Names: Androgen Deprivation Therapy
Experimental: Arm E: Zoledronic Acid & Docetaxel; (ADT + zoledronic acid + docetaxel + prednisolone) NO LONGER RECRUITING	Drug: Docetaxel; Other Names: Taxotere; Drug: Zoledronic Acid; Other Names: Zometa; Drug: Prednisolone; Other Names: Prednisone; Drug: ADT; Other Names: Androgen Deprivation Therapy
Experimental: Arm F: Zoledronic Acid & Celecoxib; (ADT + zoledronic acid + celecoxib) NO LONGER RECRUITING	Drug: Zoledronic Acid; Other Names: Zometa; Drug: Celecoxib; Other Names: Celebrex; Drug: ADT; Other Names: Androgen Deprivation Therapy
Experimental: Arm G: Abiraterone; (ADT + abiraterone acetate + prednisolone) NO LONGER RECRUITING	Drug: Prednisolone; Other Names: Prednisone; Drug: ADT; Other Names: Androgen Deprivation Therapy; Drug: Abiraterone; Other Names: Zytiga
Experimental: Arm H: M1 RT; (ADT + radiotherapy to the prostate) NO LONGER RECRUITING	Drug: ADT; Other Names: Androgen Deprivation Therapy; Radiation: Radiotherapy to the prostate; Other Names: RT
Experimental: Arm J: Abiraterone * Enzalutamide; (ADT + abiraterone + enzalutamide + Prednisolone) NO LONGER RECRUITING	Drug: Prednisolone; Other Names: Prednisone; Drug: Enzalutamide; Other Names: Xtandi; Drug: ADT; Other Names: Androgen Deprivation Therapy; Drug: Abiraterone; Other Names: Zytiga
Experimental: Arm K: Metformin; (ADT + Metformin) RECRUITING IN SELECTED SITES	Drug: Metformin; Other Names: Metformin Hydrochloride; Drug: ADT; Other Names: Androgen Deprivation Therapy
Experimental: Arm L: tE2; (Transdermal oestradiol) RECRUITING	Drug: Transdermal Oestradiol; Other Names: Progynova TS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time to mortality	1:Not applicable

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free survival	Report of time from initiation of treatment to the first progression event of each patient	1:Not applicable
Cost effectiveness by EuroQol	Reporting the comparison of costs associated with the additional treatments provided and the survival gain attributed to the additional treatments, to SOC alone.	1:Not applicable
Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item	Determination of changes in quality of life with interventions	1:Not applicable
Number of participants with treatment-related side effects as assessed by CTCAE v4.0	Reporting the incidence, type and severity of side effects within the trial population. CTCAE v4.0 will be used to classify the events names and severity.	1:Not applicable
Skeletal related events	Reporting the incidence and types of skeletal related events	1:Not applicable
Biochemical failure	For the purposes of the STAMPEDE trial, a unique threshold PSA value for biochemical failure is calculated for each patient, referred to as the PSA progression value. A. If PSA nadir in the 24 weeks following randomisation is more than 4ng/ml and more than 50% of the pre-treatment PSA level - immediate treatment failure. B. If PSA nadir in the 24 weeks following randomisation is less than or equal to 50% of the pre-treatment PSA level but remains above 4ng/ml - treatment failure will be defined as a rise of 50% above the nadir level. C. If PSA nadir in the 24 weeks following randomisation is less than or equal to 4ng/ml - treatment failure will be defined as at least 50% rise above the nadir value and also above 4ng/ml.	1:Not applicable
Progression-free survival	Reporting the incidence of mortality without a progression event	1:Not applicable
Lymph node progression	Reporting the incidence and severity of lymph node events	1:Not applicable
Distant metastases	Reporting the incidence and severity of distant metastatic events	1:Not applicable
Treatment for progression	Identifying and reporting the treatments used in second line treatment. Incidence and types of treatments.	1:Not applicable
Disease-specific survival	Reporting the mortality attributed to Prostate Cancer	1:Not applicable
Non-prostate cancer death	Reporting the mortality not attributed to Prostate Cancer	1:Not applicable
Metabolic effects	Reporting the incidence and severity of effects on metabolic systems	1:Not applicable

Collaborators and Investigators

• Sponsor: Medical Research Council
• Investigators: Study Chair: Nicholas D. James, MD, Institute of Cancer Research, United Kingdom

Publications and helpful links

General Publications

• Roy S, Malone S, Grimes S, Morgan SC. Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):181-190. doi: 10.1016/j.clon.2020.09.005. Epub 2020 Sep 29.
• Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, Heidenreich A, Skoetz N. Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis. Cochrane Database Syst Rev. 2020 Dec 3;12(12):CD013020. doi: 10.1002/14651858.CD013020.pub2.
• Sydes MR, Parmar MK, Mason MD, Clarke NW, Amos C, Anderson J, de Bono J, Dearnaley DP, Dwyer J, Green C, Jovic G, Ritchie AW, Russell JM, Sanders K, Thalmann G, James ND. Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial. Trials. 2012 Sep 15;13:168. doi: 10.1186/1745-6215-13-168.
• Sydes MR, Parmar MK, James ND, Clarke NW, Dearnaley DP, Mason MD, Morgan RC, Sanders K, Royston P. Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial. Trials. 2009 Jun 11;10:39. doi: 10.1186/1745-6215-10-39.
• Parker CC, Sydes MR, Mason MD, Clarke NW, Aebersold D, de Bono JS, Dearnaley DP, Ritchie AW, Russell JM, Thalmann G, Parmar MK, James ND. Prostate radiotherapy for men with metastatic disease: a new comparison in the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial. BJU Int. 2013 May;111(5):697-9. doi: 10.1111/bju.12087. No abstract available.
• Attard G, Sydes MR, Mason MD, Clarke NW, Aebersold D, de Bono JS, Dearnaley DP, Parker CC, Ritchie AW, Russell JM, Thalmann G, Cassoly E, Millman R, Matheson D, Schiavone F, Spears MR, Parmar MK, James ND. Combining enzalutamide with abiraterone, prednisone, and androgen deprivation therapy in the STAMPEDE trial. Eur Urol. 2014 Nov;66(5):799-802. doi: 10.1016/j.eururo.2014.05.038. Epub 2014 Jun 27.
• James ND, Spears MR, Clarke NW, Dearnaley DP, De Bono JS, Gale J, Hetherington J, Hoskin PJ, Jones RJ, Laing R, Lester JF, McLaren D, Parker CC, Parmar MKB, Ritchie AWS, Russell JM, Strebel RT, Thalmann GN, Mason MD, Sydes MR. Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019). Eur Urol. 2015 Jun;67(6):1028-1038. doi: 10.1016/j.eururo.2014.09.032. Epub 2014 Oct 6.
• James ND, Spears MR, Clarke NW, Dearnaley DP, Mason MD, Parker CC, Ritchie AW, Russell JM, Schiavone F, Attard G, de Bono JS, Birtle A, Engeler DS, Elliott T, Matheson D, O'Sullivan J, Pudney D, Srihari N, Wallace J, Barber J, Syndikus I, Parmar MK, Sydes MR; STAMPEDE Investigators. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial. JAMA Oncol. 2016 Mar;2(3):348-57. doi: 10.1001/jamaoncol.2015.4350. Erratum In: JAMA Oncol. 2016 Feb;2(2):279.
• Gillessen S, Gilson C, James N, Adler A, Sydes MR, Clarke N; STAMPEDE Trial Management Group. Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform. Eur Urol. 2016 Dec;70(6):906-908. doi: 10.1016/j.eururo.2016.07.015. Epub 2016 Jul 19.
• Gilbert DC, Duong T, Sydes M, Bara A, Clarke N, Abel P, James N, Langley R, Parmar M; STAMPEDE and PATCH Trial Management Groups. Transdermal oestradiol as a method of androgen suppression for prostate cancer within the STAMPEDE trial platform. BJU Int. 2018 May;121(5):680-683. doi: 10.1111/bju.14153. Epub 2018 Feb 28. No abstract available.
• Parmar MK, Barthel FM, Sydes M, Langley R, Kaplan R, Eisenhauer E, Brady M, James N, Bookman MA, Swart AM, Qian W, Royston P. Speeding up the evaluation of new agents in cancer. J Natl Cancer Inst. 2008 Sep 3;100(17):1204-14. doi: 10.1093/jnci/djn267. Epub 2008 Aug 26.
• James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Anderson J, Popert RJ, Sanders K, Morgan RC, Stansfeld J, Dwyer J, Masters J, Parmar MK. Systemic therapy for advancing or metastatic prostate cancer (STAMPEDE): a multi-arm, multistage randomized controlled trial. BJU Int. 2009 Feb;103(4):464-9. doi: 10.1111/j.1464-410X.2008.08034.x. Epub 2008 Oct 8.
• James ND, Sydes MR, Mason MD, Clarke NW, Anderson J, Dearnaley DP, Dwyer J, Jovic G, Ritchie AW, Russell JM, Sanders K, Thalmann GN, Bertelli G, Birtle AJ, O'Sullivan JM, Protheroe A, Sheehan D, Srihari N, Parmar MK; STAMPEDE investigators. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial. Lancet Oncol. 2012 May;13(5):549-58. doi: 10.1016/S1470-2045(12)70088-8. Epub 2012 Mar 26. Erratum In: Lancet Oncol. 2013 Jan;14(1):e5.
• Vale CL, Burdett S, Rydzewska LHM, Albiges L, Clarke NW, Fisher D, Fizazi K, Gravis G, James ND, Mason MD, Parmar MKB, Sweeney CJ, Sydes MR, Tombal B, Tierney JF; STOpCaP Steering Group. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol. 2016 Feb;17(2):243-256. doi: 10.1016/S1470-2045(15)00489-1. Epub 2015 Dec 21. Erratum In: Lancet Oncol. 2016 Feb;17(2):e46.
• Mason MD, Clarke NW, James ND, Dearnaley DP, Spears MR, Ritchie AWS, Attard G, Cross W, Jones RJ, Parker CC, Russell JM, Thalmann GN, Schiavone F, Cassoly E, Matheson D, Millman R, Rentsch CA, Barber J, Gilson C, Ibrahim A, Logue J, Lydon A, Nikapota AD, O'Sullivan JM, Porfiri E, Protheroe A, Srihari NN, Tsang D, Wagstaff J, Wallace J, Walmsley C, Parmar MKB, Sydes MR; STAMPEDE Investigators. Adding Celecoxib With or Without Zoledronic Acid for Hormone-Naive Prostate Cancer: Long-Term Survival Results From an Adaptive, Multiarm, Multistage, Platform, Randomized Controlled Trial. J Clin Oncol. 2017 May 10;35(14):1530-1541. doi: 10.1200/JCO.2016.69.0677. Epub 2017 Mar 13.
• James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, Ritchie AWS, Amos CL, Gilson C, Jones RJ, Matheson D, Millman R, Attard G, Chowdhury S, Cross WR, Gillessen S, Parker CC, Russell JM, Berthold DR, Brawley C, Adab F, Aung S, Birtle AJ, Bowen J, Brock S, Chakraborti P, Ferguson C, Gale J, Gray E, Hingorani M, Hoskin PJ, Lester JF, Malik ZI, McKinna F, McPhail N, Money-Kyrle J, O'Sullivan J, Parikh O, Protheroe A, Robinson A, Srihari NN, Thomas C, Wagstaff J, Wylie J, Zarkar A, Parmar MKB, Sydes MR; STAMPEDE Investigators. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017 Jul 27;377(4):338-351. doi: 10.1056/NEJMoa1702900. Epub 2017 Jun 3.
• Sydes MR, Spears MR, Mason MD, Clarke NW, Dearnaley DP, de Bono JS, Attard G, Chowdhury S, Cross W, Gillessen S, Malik ZI, Jones R, Parker CC, Ritchie AWS, Russell JM, Millman R, Matheson D, Amos C, Gilson C, Birtle A, Brock S, Capaldi L, Chakraborti P, Choudhury A, Evans L, Ford D, Gale J, Gibbs S, Gilbert DC, Hughes R, McLaren D, Lester JF, Nikapota A, O'Sullivan J, Parikh O, Peedell C, Protheroe A, Rudman SM, Shaffer R, Sheehan D, Simms M, Srihari N, Strebel R, Sundar S, Tolan S, Tsang D, Varughese M, Wagstaff J, Parmar MKB, James ND; STAMPEDE Investigators. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018 May 1;29(5):1235-1248. doi: 10.1093/annonc/mdy072.
• Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, Ritchie AWS, Attard G, Chowdhury S, Cross W, Dearnaley DP, Gillessen S, Gilson C, Jones RJ, Langley RE, Malik ZI, Mason MD, Matheson D, Millman R, Russell JM, Thalmann GN, Amos CL, Alonzi R, Bahl A, Birtle A, Din O, Douis H, Eswar C, Gale J, Gannon MR, Jonnada S, Khaksar S, Lester JF, O'Sullivan JM, Parikh OA, Pedley ID, Pudney DM, Sheehan DJ, Srihari NN, Tran ATH, Parmar MKB, Sydes MR; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018 Dec 1;392(10162):2353-2366. doi: 10.1016/S0140-6736(18)32486-3. Epub 2018 Oct 21.
• Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, Brawley CD, Calvert J, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert D, Gillessen S, Jones RJ, Langley RE, MacNair A, Malik Z, Mason MD, Matheson D, Millman R, Parker CC, Ritchie AWS, Rush H, Russell JM, Brown J, Beesley S, Birtle A, Capaldi L, Gale J, Gibbs S, Lydon A, Nikapota A, Omlin A, O'Sullivan JM, Parikh O, Protheroe A, Rudman S, Srihari NN, Simms M, Tanguay JS, Tolan S, Wagstaff J, Wallace J, Wylie J, Zarkar A, Sydes MR, Parmar MKB, James ND. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003. doi: 10.1093/annonc/mdz396. Erratum In: Ann Oncol. 2020 Mar;31(3):442.
• Parker CC, James ND, Brawley CD, Clarke NW, Ali A, Amos CL, Attard G, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert DC, Gilson C, Gillessen S, Hoyle A, Jones RJ, Langley RE, Malik ZI, Mason MD, Matheson D, Millman R, Rauchenberger M, Rush H, Russell JM, Sweeney H, Bahl A, Birtle A, Capaldi L, Din O, Ford D, Gale J, Henry A, Hoskin P, Kagzi M, Lydon A, O'Sullivan JM, Paisey SA, Parikh O, Pudney D, Ramani V, Robson P, Srihari NN, Tanguay J, Parmar MKB, Sydes MR; STAMPEDE Trial Collaborative Group. Radiotherapy to the prostate for men with metastatic prostate cancer in the UK and Switzerland: Long-term results from the STAMPEDE randomised controlled trial. PLoS Med. 2022 Jun 7;19(6):e1003998. doi: 10.1371/journal.pmed.1003998. eCollection 2022 Jun.
• Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Amos CL, Atako N, Pugh C, Buckner M, Chowdhury S, Malik Z, Russell JM, Gilson C, Rush H, Bowen J, Lydon A, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzoueb M, Parikh O, Robinson A, Syndikus I, Wylie J, Zarkar A, Thalmann G, de Bono JS, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022 Jan 29;399(10323):447-460. doi: 10.1016/S0140-6736(21)02437-5. Epub 2021 Dec 23.
• Rush HL, Murphy L, Morgans AK, Clarke NW, Cook AD, Attard G, Macnair A, Dearnaley DP, Parker CC, Russell JM, Gillessen S, Matheson D, Millman R, Brawley CD, Pugh C, Tanguay JS, Jones RJ, Wagstaff J, Rudman S, O'Sullivan JM, Gale J, Birtle A, Protheroe A, Gray E, Perna C, Tolan S, McPhail N, Malik ZI, Vengalil S, Fackrell D, Hoskin P, Sydes MR, Chowdhury S, Gilbert DC, Parmar MKB, James ND, Langley RE. Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial. J Clin Oncol. 2022 Mar 10;40(8):825-836. doi: 10.1200/JCO.21.00728. Epub 2021 Nov 10.
• Ali A, Hoyle A, Haran AM, Brawley CD, Cook A, Amos C, Calvert J, Douis H, Mason MD, Dearnaley D, Attard G, Gillessen S, Parmar MKB, Parker CC, Sydes MR, James ND, Clarke NW. Association of Bone Metastatic Burden With Survival Benefit From Prostate Radiotherapy in Patients With Newly Diagnosed Metastatic Prostate Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2021 Apr 1;7(4):555-563. doi: 10.1001/jamaoncol.2020.7857.
• James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, Ritchie AW, Parker CC, Russell JM, Attard G, de Bono J, Cross W, Jones RJ, Thalmann G, Amos C, Matheson D, Millman R, Alzouebi M, Beesley S, Birtle AJ, Brock S, Cathomas R, Chakraborti P, Chowdhury S, Cook A, Elliott T, Gale J, Gibbs S, Graham JD, Hetherington J, Hughes R, Laing R, McKinna F, McLaren DB, O'Sullivan JM, Parikh O, Peedell C, Protheroe A, Robinson AJ, Srihari N, Srinivasan R, Staffurth J, Sundar S, Tolan S, Tsang D, Wagstaff J, Parmar MK; STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1163-77. doi: 10.1016/S0140-6736(15)01037-5. Epub 2015 Dec 21.
• Huang X, Chau CH, Figg WD. Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures. J Hematol Oncol. 2012 Jul 2;5:35. doi: 10.1186/1756-8722-5-35.
• Grist E, Friedrich S, Brawley C, Mendes L, Parry M, Ali A, Haran A, Hoyle A, Gilson C, Lall S, Zakka L, Bautista C, Landless A, Nowakowska K, Wingate A, Wetterskog D, Hasan AMM, Akato NB, Richmond M, Ishaq S, Matthews N, Hamid AA, Sweeney CJ, Sydes MR, Berney DM, Lise S; STAMPEDE investigators; Parmar MKB, Clarke NW, James ND, Cremaschi P, Brown LC, Attard G. Accumulation of copy number alterations and clinical progression across advanced prostate cancer. Genome Med. 2022 Sep 5;14(1):102. doi: 10.1186/s13073-022-01080-4.

Helpful Links

• Trial home page

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2005
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): December 1, 2030

Study Registration Dates

• First Submitted: December 20, 2005
• First Submitted That Met QC Criteria: December 20, 2005
• First Posted (Estimate): December 22, 2005

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Adenocarcinoma of the prostate; Stage IV Prostate Cancer; Recurrent Prostate Cancer; Stage III Prostate Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens; Bone Density Conservation Agents; Cyclooxygenase 2 Inhibitors; Docetaxel; Prednisolone; Celecoxib; Estradiol; Prednisone; Metformin; Zoledronic Acid; Androgens
• Other Study ID Numbers: CDR0000455008; MRC-STAMPEDE (Other Identifier: MRC); EU-205102 (Other Identifier: EU); PR08 (Other Identifier: MRC CTU at UCL); ISRCTN78818544 (Registry Identifier: ISRCTN); 2004-000193-31 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No