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AzTrials

Prostate CancerPhase 2/3STAMPEDENCT00268476

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

A Phase 2/3 study testing Celecoxib, Docetaxel and Prednisolone in people with Prostate Cancer, run by Medical Research Council at 120 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 120 years, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Celecoxib, Docetaxel and Prednisolone
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11,992 participants
Where
120 sitesin 2 countries
Study dates
8 Jul 2005to Dec 2030
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 120 years
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

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
  1. Newly-Diagnosed Metastatic Or Node-Positive Disease At least one of:
  • Stage Tany N+ M0
  • Stage Tany Nany M+ OR
  1. 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
  1. General Inclusion Criteria Required For All Participants

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  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

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  1. Medical contraindications to the trial medications are given in Section 6
  2. For WHO performance status definitions see Appendix A
  3. 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.
  1. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment
  2. Any surgical wound (e.g. TURP) which in the judgement of the responsible clinician may interfere with or be exacerbated by protocol treatment
  3. 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
  3. 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

Trial locations and contacts

120 sites in 2 countries.

120 sites in 2 countries

United Kingdom110 sites

  • Bronglais General Hospital

    Aberystwyth, Wales, SY23 1ER

  • William Harvey Hospital

    Ashford, England, TN24 0LZ

  • Stoke Mandeville Hospital

    Aylesbury, England, HP21 8AL

  • Ayr Hospital

    Ayr, Scotland, KA6 6DX

  • Barnet General Hospital

    Barnet, EN5 3DJ

  • North Devon District Hospital

    Barnstaple, Devon, EX31 4JB

  • Basingstoke and North Hampshire NHS Foundation Trust

    Basingstoke, England, RG24 9NA

  • Royal United Hospital

    Bath, Somerset, BA1 3NG

  • Clatterbridge Centre for Oncology

    Bebington, Wirral, CH63 4JY

  • Centre for Cancer Research and Cell Biology at Queen's University Belfast

    Belfast, Northern Ireland, BT9 7AB

  • City Hospital (Birmingham)

    Birmingham, England, B18 7QH

  • Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

    Birmingham, West Midlands, B15 2TH

  • Royal Bournemouth Hospital

    Bournemouth, Dorset, BH7 7DW

  • Bradford Royal Infirmary

    Bradford, West Yorkshire, BD9 6RJ

  • Sussex Cancer Centre at Royal Sussex County Hospital

    Brighton, England, BN2 5BE

  • Bristol Haematology and Oncology Centre

    Bristol, Somerset, BS2 8ED

  • Broomfield Hospital

    Broomfield, Chelmsford, CM1 7ET

  • Burnley General Hospital

    Burnley, England, BB10 2PQ

  • Queen's Hospital

    Burton-on-Trent, England, DE13 0RB

  • West Suffolk Hospital

    Bury St Edmunds, England, IP33 2QZ

  • Addenbrooke's Hospital

    Cambridge, Cambridgeshire, CB2 0QQ

  • Kent and Canterbury Hospital

    Canterbury, Kent, CT1 3NG

  • Velindre Cancer Center at Velindre Hospital

    Cardiff, Wales, CF14 2TL

  • Cumberland Infirmary

    Carlisle, Cumbria, CA2 7HY

  • Cheltenham General Hospital

    Cheltenham, Gloucestershire, GL53 7AN

  • Countess of Chester Hospital

    Chester, Chesire, CH2 1UL

  • Colchester General Hospital

    Colchester, CO4 5JL

  • Queen Alexandra Hospital

    Cosham, Portsmouth, P06 3LY

  • Castle Hill Hospital

    Cottingham, East Riding Of Yorkshire, HU16 5JQ

  • Mid Cheshire Hospitals Trust- Leighton Hopsital

    Crewe, England, CW1 4QJ

  • Darlington Memorial

    Darlington, England, DL3 6HX

  • Derbyshire Royal Infirmary

    Derby, England, DE22 3NE

  • Doncaster Royal Infirmary

    Doncaster, England, DN2 5LT

  • Dorset County Hospital

    Dorchester, Dorset, DT1 2JY

  • Russells Hall Hospital

    Dudley, England, DY1 2HQ

  • University Hospital of North Durham

    Durham, England, DH1 5TW

  • Eastbourne District General Hospital

    Eastbourne, East Sussex, BN21 2UD

  • Edinburgh Cancer Centre at Western General Hospital

    Edinburgh, Midlothian, EH4 2XU

  • Royal Devon and Exeter Hospital

    Exeter, Devon, EX2 5DW

  • Royal Bolton Hospital

    Farnworth, Bolton, BL4 0JR

  • Beatson Institute for Cancer Research - Glasgow

    Glasgow, Lanarkshire, G12 0YN

  • Gloucestershire Royal Hospital

    Gloucester, England, GL1 3NN

  • St. Luke's Cancer Centre at Royal Surrey County Hospital

    Guildford, Surrey, GU2 7XX

  • Princess Alexandra Hospital

    Harlow, Essex, CM20 1QX

  • Hereford County Hospital

    Hereford, England, HR1 2ER

  • Wycombe General Hospital

    High Wycombe, Buckinghamshire, HP11 2TT

  • Huddersfield Royal Infirmary

    Huddersfield, West Yorkshire, HD3 3EA

  • Raigmore Hospital

    Inverness, Highland, IV2 3UJ

  • Ipswich Hospital

    Ipswich, Suffolk, IP4 5PD

  • Kidderminster Hospital

    Kidderminster, England, DY11 6RJ

  • Forth Valley Hospital

    Larbert, FK5 4WR

  • Leeds Cancer Centre at St. James's University Hospital

    Leeds, England, LS9 7TF

  • Glenfield Hospital

    Leicester, England

  • Lincoln Hospital

    Lincoln, LN2 5QY

  • Royal Liverpool University Hospital

    Liverpool, England, L7 8XP

  • University Hospital Aintree

    Liverpool, England, L9 7AL

  • Helen Rollason Cancer Care Centre at North Middlesex Hospital

    London, England, N18 1QX

  • Guy's Hospital

    London, England, SE1 9RT

  • St. Mary's Hospital

    London, England, W2 1NY

  • UCL Cancer Institute

    London, England, WC1E 6DD

  • University College of London Hospitals

    London, England, WIT 3AA

  • St. Bartholomews Hospital

    London, Greater London, EC1A 7BE

  • Queen Elizabeth Hospital - Woolwich

    London, Greater London, SE18 4QH

  • St. George's Hospital

    London, Greater London, SW17 0QT

  • Charing Cross Hospital

    London, Greater London, W6 8RF

  • Mid Kent Oncology Centre at Maidstone Hospital

    Maidstone, Kent, ME16 9QQ

  • Withington Hospital

    Manchester, England, M20 8LR

  • Christie Hospital

    Manchester, Greater Manchester, M20 4BX

  • Queen Elizabeth The Queen Mother Hospital

    Margate, Kent, CT9 4AN

  • James Cook University Hospital

    Middlesbrough, County Durham, TS4 3BW

  • Freeman Hospital

    Newcastle, Newcastle-upon-Tyne, NE7 7DN

  • Northern Centre for Cancer Treatment at Newcastle General Hospital

    Newcastle upon Tyne, Tyne & Wear, NE4 6BE

  • St. Mary's Hospital

    Newport, Isle Of Wight, PO30 5TG

  • Mount Vernon Cancer Centre at Mount Vernon Hospital

    Northwood, Middlesex, HA6 2RN

  • Nottingham City Hospital

    Nottingham, Nottinghamshire, NG5 1PB

  • Royal Oldham Hospital

    Oldham, Greater Manchester, OL1 2JH

  • Churchill Hospital

    Oxford, Oxfordshire, OX3 7LE

  • Poole Hospital

    Poole, Dorset, BH15 2JB

  • Rosemere Cancer Centre at Royal Preston Hospital

    Preston, Lancashire, PR2 4QF

  • Berkshire Cancer Centre at Royal Berkshire Hospital

    Reading, Berkshire, RG1 5AN

  • Queen's Hospital

    Romford, Essex, RM7 0AG

  • Conquest Hospital

    Saint Leonards-on-Sea, East Sussex, TN37 7PT

  • Scarborough General Hospital

    Scarborough, North Yorkshire, YO12 6QL

  • Cancer Research Centre at Weston Park Hospital

    Sheffield, South Yorkshire, S10 2SJ

  • Royal Shrewsbury Hospital

    Shrewsbury, England, SY3 8XQ

  • South Tyneside District Hospital

    South Shields, Tyne & Wear, NE34 0PL

  • Southampton General Hospital

    Southampton, Hampshire, S016 6YD

  • Southport and Formby District General Hospital

    Southport, Merseyside, PR8 6PN

  • Airedale General Hospital

    Steeton, Keighley, BD20 6TD

  • Lister Hospital

    Stevenage, Hertfordshire, SG1 4AB

  • Stepping Hill Hospital

    Stockport, England, SK2 7JE

  • North Tees Hospital

    Stockton-on-Tees, TS19 8PE

  • Royal Stoke University Hospital

    Stoke-on-Trent, Staffordshire, ST4 6QG

  • Sunderland Royal Hospital

    Sunderland, England, SR4 7TP

  • Royal Marsden - Sutton

    Sutton, Surrey, SM2 5PT

  • Good Hope Hospital

    Sutton Coldfield, West Midlands, B75 7RR

  • King's Mill Hospital

    Sutton in Ashfield, Nottinghamshire, NG17 4JL

  • South West Wales Cancer Institute At Singleton Hospital

    Swansea, Glamorgan, SA2 8QA

  • Great Western Hospital

    Swindon, Wiltshire, SN3 6BB

  • Musgrove Park Hospital

    Taunton, Somerset, TA1 5DA

  • Torbay Hospital

    Torquay, England, TQ2 7AA

  • Warrington Hospital NHS Trust

    Warrington, England, WA5 1QG

  • Southend University Hospital NHS Foundation Trust

    Westcliff-on-Sea, Essex, SS0 0RY

  • Weston General Hospital

    Weston-super-Mare, Somerset, BS23 4TQ

  • West Cumberland Hospital

    Whitehaven, England, CA28 8JG

  • Royal Albert Edward Infirmary

    Wigan, England, WN1 2NN

  • New Cross Hospital

    Wolverhampton, WV10 0QP

  • Worcester Royal Hospital

    Worcester, England, WR5 1DD

  • Worthing Hospital

    Worthing, England, BN11 2DH

  • Yeovil District Hospital

    Yeovil, Somerset, BA21 4AT

Other trials in United Kingdom

Switzerland10 sites

  • Hirslanden Klinik Aarau

    Aarau, CH-5000

  • Universitaetsspital-Basel

    Basel, CH-4031

  • Inselspital Bern

    Bern, CH-3010 Be

  • Kantonsspital Graubuenden

    Chur, Kanton Graubünden, CH-7000

  • Lausanne Centre Hospitalier Universitaire

    Lausanne, Canton of Vaud, CH-1011

  • Liestal Hospital

    Liestal, CH-4410

  • Kantonsspital - St. Gallen

    Sankt Gallen, CH-9007

  • Winterthur Hospital

    Winterthur, Canton of Zurich, CH-8401

  • UniversitaetsSpital Zuerich

    Zurich, CH-8091

  • City Hospital Triemli

    Zurich

Other trials in Switzerland

About this study

Official title: 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.

Read more

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.
Read the 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.

Conditions
Prostate Cancer
Keywords
Stage III Prostate Cancer, Stage IV Prostate Cancer, Recurrent Prostate Cancer, Adenocarcinoma of the prostate
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CelecoxibDrug

    Also called Celebrex

  • DocetaxelDrug

    Also called Taxotere

  • PrednisoloneDrug

    Also called Prednisone

  • ADTDrug

    Also called Androgen Deprivation Therapy

  • Zoledronic AcidDrug

    Also called Zometa

  • AbirateroneDrug

    Also called Zytiga

  • Radiotherapy to the prostateRadiation

    Also called RT

  • EnzalutamideDrug

    Also called Xtandi

  • MetforminDrug

    Also called Metformin Hydrochloride

  • Transdermal OestradiolDrug

    Also called Progynova TS

Study groups in NCT00268476
Study groupRoleWhat they receive
Arm A: Standard of CareActive comparatorAndrogen Deprivation Therapy [ADT] (plus Radiotherapy for newly-diagnosed non-metastatic disease, plus or minus Docetaxel, plus or minus Abiraterone)[Control]
Receives: Drug: ADT
Arm B: Zoledronic AcidExperimental(ADT + zoledronic acid) NO LONGER RECRUITING
Receives: Drug: ADT; Drug: Zoledronic Acid
Arm C: DocetaxelExperimental(ADT + docetaxel + prednisolone) NO LONGER RECRUITING
Receives: Drug: Docetaxel; Drug: Prednisolone; Drug: ADT
Arm D: CelecoxibExperimental(ADT + celecoxib) NO LONGER RECRUITING
Receives: Drug: Celecoxib; Drug: ADT
Arm E: Zoledronic Acid & DocetaxelExperimental(ADT + zoledronic acid + docetaxel + prednisolone) NO LONGER RECRUITING
Receives: Drug: Docetaxel; Drug: Prednisolone; Drug: ADT; Drug: Zoledronic Acid
Arm F: Zoledronic Acid & CelecoxibExperimental(ADT + zoledronic acid + celecoxib) NO LONGER RECRUITING
Receives: Drug: Celecoxib; Drug: ADT; Drug: Zoledronic Acid
Arm G: AbirateroneExperimental(ADT + abiraterone acetate + prednisolone) NO LONGER RECRUITING
Receives: Drug: Prednisolone; Drug: ADT; Drug: Abiraterone
Arm H: M1 RTExperimental(ADT + radiotherapy to the prostate) NO LONGER RECRUITING
Receives: Drug: ADT; Radiation: Radiotherapy to the prostate
Arm J: Abiraterone * EnzalutamideExperimental(ADT + abiraterone + enzalutamide + Prednisolone) NO LONGER RECRUITING
Receives: Drug: Prednisolone; Drug: ADT; Drug: Abiraterone; Drug: Enzalutamide
Arm K: MetforminExperimental(ADT + Metformin) RECRUITING IN SELECTED SITES
Receives: Drug: ADT; Drug: Metformin
Arm L: tE2Experimental(Transdermal oestradiol) RECRUITING
Receives: Drug: Transdermal Oestradiol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Time to mortality

    Measured: 1:Not applicable

Secondary outcomes (13)

  1. Failure-free survival

    Report of time from initiation of treatment to the first progression event of each patient

    Measured: 1:Not applicable

  2. 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.

    Measured: 1:Not applicable

  3. Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item

    Determination of changes in quality of life with interventions

    Measured: 1:Not applicable

  4. 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.

    Measured: 1:Not applicable

  5. Skeletal related events

    Reporting the incidence and types of skeletal related events

    Measured: 1:Not applicable

  6. 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.

    1. 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.
    2. 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.
    3. 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.

    Measured: 1:Not applicable

  7. Progression-free survival

    Reporting the incidence of mortality without a progression event

    Measured: 1:Not applicable

  8. Lymph node progression

    Reporting the incidence and severity of lymph node events

    Measured: 1:Not applicable

  9. Distant metastases

    Reporting the incidence and severity of distant metastatic events

    Measured: 1:Not applicable

  10. Treatment for progression

    Identifying and reporting the treatments used in second line treatment. Incidence and types of treatments.

    Measured: 1:Not applicable

  11. Disease-specific survival

    Reporting the mortality attributed to Prostate Cancer

    Measured: 1:Not applicable

  12. Non-prostate cancer death

    Reporting the mortality not attributed to Prostate Cancer

    Measured: 1:Not applicable

  13. Metabolic effects

    Reporting the incidence and severity of effects on metabolic systems

    Measured: 1:Not applicable

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2005 (estimated)
  2. Study start8 Jul 2005
  3. Primary completionMar 2026 (estimated)
  4. Study completionDec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multi-arm Multi-Stage
Masking
None (open label)
Enrolment
11,992 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00268476
Sponsor's protocol ID
CDR0000455008
Other IDs
MRC-STAMPEDE, EU-205102, PR08, ISRCTN78818544, 2004-000193-31, 2004
Acronym
STAMPEDE
Status last verified
Apr 2023
First submitted
20 Dec 2005
Last updated
18 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 19519885

  • 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.

    PubMed 22978443

  • 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.

    PubMed 23578233

  • 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.

    PubMed 24985962

  • 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.

    PubMed 25301760

  • 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.

    PubMed 26606329

  • 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.

    PubMed 27450106

  • 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.

    PubMed 29388336

  • 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.

    PubMed 18728279

  • 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.

    PubMed 18990168

  • 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.

    PubMed 22452894

  • 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.

    PubMed 26718929

  • 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.

    PubMed 28300506

  • 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.

    PubMed 28578639

  • 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.

    PubMed 29529169

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Celecoxib, Docetaxel and Prednisolone in people with Prostate Cancer, run by Medical Research Council at 120 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 120 sites in United Kingdom, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: 1:Not applicable). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00268476, which also lists 33 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2023.

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