Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of ... | Recruiting
Systemic Therapy in Advancing or Me... | Recruiting
Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy
STAMPEDE

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Medical Conditions
  • Prostate Cancer
Primary Contact Details
STAMPEDE Trial Team
+44 (0)20 7670 4700
See all trial contact details
Recruitment Status
Recruiting
Trial source and source ID number
NCT00268476
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
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. 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.
Research Details
  • 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.
Phase
Phase 2/Phase 3
Study Design
Sorry, this information is not available
Study Type
Interventional
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

Study Arm Groups : Arm D: Celecoxib, Arm F: Zoledronic Acid & Celecoxib, Arm C: Docetaxel, Arm E: Zoledronic Acid & Docetaxel, Arm C: Docetaxel, Arm E: Zoledronic Acid & Docetaxel, Arm G: Abiraterone, Arm J: Abiraterone * Enzalutamide, Arm A: Standard of Care, Arm B: Zoledronic Acid, Arm C: Docetaxel, Arm D: Celecoxib, Arm E: Zoledronic Acid & Docetaxel, Arm F: Zoledronic Acid & Celecoxib, Arm G: Abiraterone, Arm H: M1 RT, Arm J: Abiraterone * Enzalutamide, Arm K: Metformin, Arm B: Zoledronic Acid, Arm E: Zoledronic Acid & Docetaxel, Arm F: Zoledronic Acid & Celecoxib, Arm G: Abiraterone, Arm J: Abiraterone * Enzalutamide, Arm H: M1 RT, Arm J: Abiraterone * Enzalutamide, Arm K: Metformin, Arm L: tE2

Intervention Type
See Interventions above
Primary Outcome Measures
    Overall survival; 1:Not applicable
Secondary Outcome Measures
    Failure-free survival; 1:Not applicable; Cost effectiveness by EuroQol; 1:Not applicable; Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item; 1:Not applicable; Toxicity; 1:Not applicable; Skeletal related events; 1:Not applicable; Biochemical failure; 1:Not applicable; Progression-free survival; 1:Not applicable; Lymph node progression; 1:Not applicable; Distant metastases; 1:Not applicable; Treatment for progression; 1:Not applicable; Disease-specific survival; 1:Not applicable; Non-prostate cancer death; 1:Not applicable; Metabolic effects; 1:Not applicable
Publication(s)
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.; 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. Erratum in: Lancet Oncol. 2013 Jan;14(1):e5.; 22452894
Result Reports
Check availability of results on the Clinicaltrials.gov website
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Gender
Male
Age Range
N/A - 120 Years
Who Can Participate
Patients
Number of Participants
11200
Participant Inclusion Criteria
    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. Serum potassium ≥3.5mmol/L

    9. Written informed consent

    10. Willing and expected to comply with follow-up schedule

    11. 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. Patients with significant cardiovascular disease such that, in the investigator's opinion, the patient is unfit for any of the study treatments. This might include:

    •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 (NYHA II-IV)3

    •Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 6 months prior to randomisation

    •Patients with uncontrolled hypertension defined as systolic BP greater or equal than 160mmHg or diastolic BP greater or equal than 95mmHg5

    7. Prior chemotherapy for prostate cancer (excluding patients receiving docetaxel as part of the new SOC)

    8. Prior exposure to long-term hormone therapy before randomisation

    9. Prior exposure to systemic treatment for prostate cancer (excluding hormone therapy) e.g. abiraterone and enzalutamide.

    3 NYHA classifications can be found in Appendix A

    5 Based on representative values, as judged by the investigator

    For Randomisation to the "Metformin Comparison"

    Patients with known diabetes mellitus are not eligible for randomisation to the "metformin comparison". All non-diabetic patients require an HbA1c to be performed prior to randomisation (ideal timeline: within 8 weeks prior to randomisation), to confirm their non-diabetic status.

    In addition, an assessment of renal function is required to determine glomerular filtration rate (GFR). The method used to determine glomerular filtration rate may vary according local practice. Equations that either estimate glomerular filtration rate (eGFR) or creatinine clearance (CrCl) may be used and the same threshold value applies. In summary, additional inclusion criteria specifically for the "metformin comparison" are

    •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

    - Except Switzerland, please refer to SAKK appendix for local guidance

    Note that if the patient is known to be diabetic or the patient is found to have diabetes mellitus (i.e. HbA1c is 6.5% or higher) following screening, the patient is only eligible for randomisation if they meet all of the selection criteria for the "transdermal oestradiol comparison" (randomisation between Arms A and L only) All patients with abnormal baseline HbA1c (i.e. 6.0% or higher) should be informed and referred to their GP for further management.

    Where possible, the screening bloods, including HbA1c, should be performed prior to commencing SOC docetaxel. This is to reduce the likelihood of corticosteroid-related hyperglycaemia impacting on eligibility for the "metformin comparison".

    For Randomisation To The "Transdermal Oestradiol Comparison"

    Patients who have any of the following are not eligible for the "transdermal oestradiol comparison":

    •>8 weeks of anti-androgen use

    •>1 dose of monthly or 4 weekly LHRH agonist/antagonist

    - Prior LHRH agonist injection with a stated duration of effect greater than 1 month •>12 weeks since first dose of any hormone therapy

    - Bilateral orchidectomy

    - Cyproterone acetate started prior to randomisation

    - Known porphyria

    - Any history of deep vein thrombosis or pulmonary embolism confirmed radiologically

    - Known thrombophilic disorder (e.g. Protein C, protein S, antithrombin deficiency)

    Note that patients unsuitable for the "transdermal oestradiol comparison" will only be eligible for randomisation if they meet all of the selection criteria for the "metformin comparison" and therefore may be allocated to control (arm A) or metformin (arm K) only.
Participant Exclusion Criteria
This is in the inclusion criteria above
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Trial Location(s)
GSK Investigational Site
London
W2 1NY
Manchester
M20 4BX
West Suffolk Hospital
Bury Saint Edmunds
England
IP33 2QZ
Kent and Canterbury Hospital
Canterbury
England
CT1 3NG
Royal Devon and Exeter Hospital
Exeter
England
EX2 5DW
St. George's Hospital
London
England
SW17 0QT
Maidstone Hospital
Maidstone
England
ME16 9QQ
Mount Vernon Cancer Centre at Mount Vernon Hospital
Northwood
England
HA6 2RN
Royal Marsden - Surrey
Sutton
England
SM2 5PT
Torbay Hospital
Torquay
England
TQ2 7AA
Worcester Royal Hospital
Worcester
England
WR5 1DD
Edinburgh Cancer Centre at Western General Hospital
Edinburgh
Scotland
EH4 2XU
Velindre Cancer Center at Velindre Hospital
Cardiff
Wales
CF14 2TL
London
EC1A 7BE
South West Wales Cancer Institute
Sketty
Wales
SA2 8QA
GSK Investigational Site
Cambridge
CB2 0QQ
Birmingham
B15 2TH
Ipswich Hospital NHS Trust - Department of Clinical Neurology
Ipswich
IP4 5PD
St. James University Hospital, Department of Neurology
Leeds
LS9 7TF
Guy's Hospital
London
SE1 9RT
Rheumatology Department, Poole Hospital NHS Trust
Poole
BH15 2JB
Nottingham
Nottinghamshire
NG5 1PB
Belfast
BT9 7AB
Kennedy Institute Clinical Trials Unit, 4Wl, Charing Cross Hospital
London
W6 8RF
Sunderland Royal Hospital
Sunderland
Tyne and Wear
SR4 7TP
Novartis Investigative Site
Cheltenham
Gloucestershire
GL53 7AN
Novartis Investigative Site
Huddersfield
HD3 3EA
Novartis Investigative Site
Wolverhampton
WV10 0QP
Doncaster
DN2 5LT
Aylesbury
HP21 8AL
Basingstoke
RG24 9NA
Brighton
BN2 5BE
Chester
CH2 1UL
Crewe
CW1 4QJ
Darlington
DL3 6HX
Derby
DE22 3NE
Dudley
DY1 2HQ
Eastbourne
BN21 2UD
Guildford
GU2 7XX
Liverpool
L9 7AL
London
SE18 4QH
Reading
RG1 5AN
Southport
PR8 6PN
Stevenage
SG1 4AB
Swindon
SN3 6BB
Worthing
BN11 2DH
Romford
Essex
RM7 0AG
Liverpool
Merseyside
L7 8XP
Inverness
IV2 3UJ
Newcastle upon Tyne
NE7 7DN
Royal United Hospital
Bath
England
BA1 3NG
Lincoln County Hospital
Lincoln
England
LN2 5QY
Bristol
BS2 8ED
Southend NHS Trust Hospital
Southend-on-Sea
England
SS0 0RY
Taunton
TA1 5DA
Bradford
BD9 6RJ
Stockton-on-Tees
TS19 8PE
Royal Bournemouth Hospital
Bournemouth
Dorset
BH7 7DW
Uni Hospital Leicester
Leicester
Burnley
BB10 2PQ
Churchill Hospital
Oxford
OX3 7LE
City Hospital - Birmingham
Birmingham
England
B18 7QH
GSK Investigational Site
Cottingham
HU16 5JQ
Colchester General Hospital
Mile End
CO4 5JL
Sheffield
S10 2SJ
Gloucestershire Royal Hospital
Gloucester
England
GL1 3NN
Middlesbrough
TS4 3BW
Glasgow
G12 0YN
Local Institution
Newport
Isle of Wight
PO30 5TG
Hereford
HR1 2ER
Yeovil Disctrict Hospital NHS Foundation Trust
Yeovil
Somerset
BA21 4AT
Middlesex Hospital- Meyerstein Institute
London
England
WIT 3AA
Site Reference ID/Investigator# 125689
Barnstaple
EX31 4JB
Site Reference ID/Investigator# 125695
Birkenhead
CH63 4JY
Carlisle
CA2 7HY
Stockport
SK2 7JE
Queens Hospital
Burton-on-Trent
England
DE13 0RB
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Stoke-on-Trent
ST4 6QG
Dorset County Hospital
Dorchester
England
DT1 2JY
University Hospital of North Durham
Durham
England
DH1 5TW
Queen Elizabeth The Queen Mother Hospital
Margate
England
CT9 4AN
Scarborough General Hospital
Scarborough
England
YO12 6QL
Royal Shrewsbury Hospital
Shrewsbury
England
SY3 8XQ
South Tyneside District Hospital
South Shields
England
NE34 0PL
Manchester
M20 8LR
Wigan
WN1 2NN
Novartis Investigative Site
Oldham
Lancashire
OL1 2JH
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Barnet
Herts
EN5 3DJ
North Middlesex NHS Trust
London
N18 1QX
Wycombe Hospital
High Wycombe
Buckinghamshire
HP11 2TT
Broomfield Hospital
Broomfield
England
CM1 7ET
Warrington Hospital NHS Trust
Warrington
England
WA5 1QG
West Cumberland Hospital
Whitehaven
England
CA28 8JG
Northern Centre for Cancer Treatment at Newcastle General Hospital
Newcastle upon Tyne
England
NE4 6BE
University Hospital Southampton NHS Foundation Trust
Southampton
Hampshire
S016 6YD
Bronglais District General Hospital
Aberystwyth
Wales
SY23 1ER
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Harlow
CM20 1QX
Kidderminster General Hospital
Kidderminster
DY11 6RJ
Weston-super-Mare
BS23 4TQ
Channel day surgery unit
Willesborough
Kent
TN24 0LZ
Steeton
Keighley
BD20 6TD
Royal Preston Hospital
Preston
England
PR2 4QF
Ayr Hospital
Ayr
Scotland
KA6 6DX
Sutton-in-Ashfield
NG17 4JL
UCL Cancer Institute
London
England
WC1E 6DD
Forth Valley Royal Hospital
Larbert
Falkirk
FK5 4WR
GSK Clinical Trials Call Center
Sutton Coldfield
B75 7RR
Royal Bolton Hospital
Farnworth
England
BL4 0JR
Conquest Hospital
Saint Leonards-on-Sea
East Sussex
TN37 7PT
Queen Alexandra Hospital
Cosham
Portsmouth
P06 3LY
Trial Contact(s)
Primary Trial Contact
STAMPEDE Trial Team
+44 (0)20 7670 4700
Other Trial Contacts
Sorry, this information is not available
Countries Recruiting
Switzerland, United Kingdom
This information is designed to help you decide whether this trial is of interest. In some cases it is provided as a link to more detailed patient information or it may still be awaited from the organisation running the trial. Please look again shortly if the information you need is not here or, if named, contact the researcher named above.
Scientific Title
STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial
EudraCT Number
Not available for this trial
Funder(s)
    Sorry, this information is not available
Other Study ID Numbers
CDR0000455008
Sponsor(s)
Medical Research Council
Key Dates

Recruitment Start Date

Jul 2005

Recruitment End Date

Sep 2024

Trial Start Date
Date Not Available
Trial End Date
Date Not Available
Date added to source

20 Dec 2005

Date updated in source

27 Mar 2018