STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Eval... | Recruiting
STAMPEDE: Systemic Therapy in Advan... | Recruiting
STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial
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
Prostate cancers need the male hormone testosterone to grow. Hormone treatments work by stopping testosterone from reaching prostate cancer cells. There are different types of hormone treatments but the most common are injections or implants that work by stopping the testicles making testosterone. Some men will have an operation to remove a part or all of the testicles instead. This type of treatment is called hormone treatment or androgen deprivation therapy (ADT) and it is part of the current standard approach to the treatment of locally advanced or metastatic prostate cancer. In addition, radiotherapy to the prostate and or docetaxel chemotherapy may be recommended as part of the current standard-of-care.

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 16.0 onwards (activated in June 2017) 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, Procedure : Orchiectomy, Radiation : Radiotherapy to the prostate, Drug : Enzalutamide, Drug : Metformin, Drug : Transdermal Oestradiol

Study Arm Groups : Arm F (ADT + zoledronic acid + celecoxib), Arm G (ADT + abiraterone), Arm C (ADT + docetaxel + prednisolone), Arm D (ADT + celecoxib), Arm C (ADT + docetaxel + prednisolone), Arm D (ADT + celecoxib), Arm J (ADT + abiraterone + enzalutamide), Arm A Androgen Deprivation Therapy [ADT], Arm B (ADT + zoledronic acid), Arm C (ADT + docetaxel + prednisolone), Arm D (ADT + celecoxib), Arm E (ADT + zoledronic acid + docetaxel + prednisolone), Arm F (ADT + zoledronic acid + celecoxib), Arm G (ADT + abiraterone), Arm H (ADT + radiotherapy to the prostate), Arm J (ADT + abiraterone + enzalutamide), Arm B (ADT + zoledronic acid), Arm D (ADT + celecoxib), Arm E (ADT + zoledronic acid + docetaxel + prednisolone), Arm J (ADT + abiraterone + enzalutamide), Arm A Androgen Deprivation Therapy [ADT], Arm B (ADT + zoledronic acid), Arm C (ADT + docetaxel + prednisolone), Arm D (ADT + celecoxib), Arm E (ADT + zoledronic acid + docetaxel + prednisolone), Arm F (ADT + zoledronic acid + celecoxib), Arm G (ADT + abiraterone), Arm H (ADT + radiotherapy to the prostate), Arm H (ADT + radiotherapy to the prostate), Arm J (ADT + abiraterone + enzalutamide), Arm K (ADT+/- prostate RT +/- docetaxel + Metformin), Arm L (Transdermal oestradiol +/- RT +/- docetaxel)

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
8100
Participant Inclusion Criteria
    GENERAL INCLUSION CRITERIA

    To be eligible participants must fulfil the criteria within one of the broad disease categories below:

    1. High-Risk Newly-Diagnosed Non-Metastatic Node-Negative Disease (N0M0, with at least two of: T category T3/4, PSA≥40ng/ml or Gleason sum score 8-10 and intention to treat with radical radiotherapy (unless there is a contra-indication; exemption can be sought in advance of consent, after discussion with CTU)

    2. Newly-Diagnosed Non-Metastatic Node-Positive Disease (T any N+ M0)

    3. Newly-Diagnosed metastatic (T any N any M+)

    4. Previously Radically Treated, Now Relapsing (Prior Radical Surgery And/Or Radiotherapy): with at least one of: M1, N+, PSA ≥4ng/ml and rising with doubling time less than 6 months; PSA ≥20ng/ml)

    In addition all patients must meet the following criteria:

    I. Histologically confirmed prostate adenocarcinoma

    II. Intention to treat with long-term androgen deprivation therapy

    III. Treating clinician and patient should have decided if docetaxel is to be part of the standard-of-care prior to randomisation

    IV. Fit for all protocol treatment and follow-up, WHO performance status 0-2

    V. Have completed the appropriate investigations prior to randomisation

    VI. Adequate haematological function: neutrophil count >1.5x109 /l and platelets >100x109 /l

    VII. Adequate renal function, defined as GFR >30ml/min/1.73m 2

    VIII. Serum potassium ≥3.5mmol/L

    IX. Written informed consent

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

    XI. Using effective contraceptive method if applicable

    Patients must not fulfil any of the following general exclusion criteria

    I. Prior systemic therapy for locally-advanced or metastatic prostate cancer (except previously radically treated, now relapsing patients (prior radical surgery and/ or radiotherapy)

    II. Metastatic brain disease or leptomeningeal disease

    III. 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

    IV. Any other previous or current malignant disease which, in the judgement of the responsible clinician, is likely to interfere with STAMPEDE treatment or assessment

    V. Any surgery (e.g. TURP) performed within the past 4 weeks

    VI. 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 • 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 95mmHg (based on representative values as judged by the investigator)

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

    VIII. Prior exposure to long-term hormone therapy before randomisation. (Any patients now presenting with relapsed disease, previously treated with adjuvant or neo adjuvant hormone therapy alongside their radical surgery or radiotherapy, must have completed that period of hormone therapy at least 12 months before joining STAMPEDE and it must have been no longer than 12 months in duration).

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

    Comparison-Specific Selection Criteria

    To be eligible for randomisation to the "metformin comparison" patients must fulfil the following criteria:

    - 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

    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, prostein S, antithrombin deficiency)
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)
Local Institution
Cambridge
Cambridgeshire
Local Institution
Glasgow
Central
Local Institution
London
Greater London
Local Institution
Northwood
Middlesex
Local Institution
Oxford
Oxfordshire
West Suffolk Hospital
Bury Saint Edmunds
England
IP33 2QZ
Torbay Hospital
Torquay
England
TQ2 7AA
Worcester Royal Hospital
Worcester
England
WR5 1DD
Velindre Cancer Center at Velindre Hospital
Cardiff
Wales
CF14 2TL
Manchester
Belfast
Edinburgh
Queen Elizabeth Hospital
Birmingham
Heart & Chest Hospital
Liverpool
Sunderland Royal Hospital
Sunderland
Tyne and Wear
SR4 7TP
Sheffield
Aylesbury
HP21 8AL
Brighton
BN2 5BE
Worthing
BN11 2DH
Sanofi-Aventis Administrative Office
Guildford
Local Institution
Newcastle upon Tyne
Tyne and Wear
Oldfield Surgery
Bath
Greenwood Medical Center
Nottingham
Reading Clinical Research Centre
Reading
Brook Lane Surgery
Southampton
Leeds
Sutton
Hull Clinical Trials Unit
Cottingham
East Yorkshire
Uni Hospital Leicester
Leicester
Uni Hospital North Staffordshire
Stoke-on-Trent
Great Western Hospital
Swindon
Derby
Preston
Bristol
SalfordRoyal NHS Foundation Trust
Salford
Bradford Royal Infirmary
Bradford
NHS Forth Valley Hospital
Larbert
Research Site
Ipswich
Hereford Hospital
Hereford
Dudley
Exeter
Inverness
Taunton
North Hampshire & Basingstoke Hospital
Basingstoke
Royal Bournemouth
Bournemouth
Cheltenham General Hospital and Gloucestershire Royal Infirmary
Cheltenham
Colchester General Hospital
Colchester
Doncaster Royal Infirmary
Doncaster
Lincoln County Hospital, Pilgrim Hospital, Grantham and District Hospital
Lincoln
Maidstone Hospital and The Tunbridge Wells Hospital
Maidstone
The James Cook University Hospital
Middlesbrough
Royal Oldham
Oldham
Queen's Hospital
Romford
Ayr
Burnley
Swansea
Weston-super-Mare
Research Site
Southend-on-Sea
Middlesex Hospital- Meyerstein Institute
London
England
WIT 3AA
Local Institution
Newport
Gwent
Stockport
SK2 7JE
Research Site
Wolverhampton
University Hospital of North Durham
Durham
England
DH1 5TW
Wycombe General Hospital
High Wycombe
England
Manchester
M20 8LR
Investigative site
Eastbourne
Leighton Hospital
Crewe
Darlington
Royal Preston Hospital
Lancashire
Barnet
Warrington Hospital NHS Trust
Warrington
England
WA5 1QG
Research Site
Newcastle upon Tyne
Research Site
Stevenage
Countess of Chester Hospital
Chester
Cheshire
Dorset County Hospital
Dorchester
Dorset
Kent and Canterbury Hospital
Canterbury
Kent
Queens Hospital
Burton upon Trent
Staffordshire
Airdale General Hospital
Keighley
West Yorkshire
Research Site
Whitehaven
Gloucestershire Royal Hospital
Gloucester
Research Site
Essex
Merseyside
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Shrewsbury
Shropshire
Channel day surgery unit
Willesborough
Kent
TN24 0LZ
Research Site
Barnstaple
Devon
UCL Cancer Institute
London
England
WC1E 6DD
Novartis Investigative Site
Farnworth
Southport and Ormskirk
Southport
Cumberland Infirmary
Carlisle
University Hospital Of North Tees
Stockton-on-Tees
South Shields
Queen Elizabeth The Queen Mother Hospital
Margate
England
Mid Essex Hospitals - Broomfield Hospital
Broomfield
Research Site
Scarborough
Queen Alexandra Hospital
Portsmouth
England
Huddersfield Royal Infirmary
Huddersfield
England
Dorset Cancer Centre
Poole
England
Conquest Hospital
Saint Leonards
England
King's Mill Hospital
Sutton-in-Ashfield
England
Bronglais General Hospital
Aberystwyth
Wales
Yeovil District Hospital
Yeovil
Kidderminster Hospital
Kidderminster
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 Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy - Androgen Suppression-Based Therapy Alone or Combined With Zoledronic Acid, Docetaxel, Prednisolone, Celecoxib, Abiraterone, Enzalutamide and/or Radiotherapy, Metformin and Transdermal Oestradiol in Treating Patients With Locally Advanced or Metastatic Prostate Cancer
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

Sep 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

21 Sep 2017