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

Prostate Cancer Clinical Trial

— STAMPEDE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00268476
• Other study ID #: CDR0000455008
• Secondary ID: MRC-STAMPEDEEU-2
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: July 8, 2005
• Est. completion date: December 2030

Study information

• Verified date: April 2023
• Source: Medical Research Council
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11992
• Est. completion date: December 2030
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Celecoxib

• Docetaxel

• Prednisolone

• ADT

• Zoledronic Acid

• Abiraterone

Radiation:
• Radiotherapy to the prostate

Drug:
• Enzalutamide

• Metformin

• Transdermal Oestradiol

Locations

Country	Name	City	State
Switzerland	Hirslanden Klinik Aarau	Aarau
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Inselspital Bern	Berne
Switzerland	Kantonsspital Graubuenden	Chur	Graubunden
Switzerland	Lausanne Centre Hospitalier Universitaire	Lausanne	Vaud
Switzerland	Liestal Hospital	Liestal
Switzerland	Kantonsspital - St. Gallen	St. Gallen
Switzerland	Winterthur Hospital	Winterthur	Zurich
Switzerland	City Hospital Triemli	Zurich
Switzerland	UniversitaetsSpital Zuerich	Zurich
United Kingdom	Bronglais General Hospital	Aberystwyth	Wales
United Kingdom	William Harvey Hospital	Ashford	England
United Kingdom	Stoke Mandeville Hospital	Aylesbury	England
United Kingdom	Ayr Hospital	Ayr	Scotland
United Kingdom	Barnet General Hospital	Barnet
United Kingdom	North Devon District Hospital	Barnstaple	Devon
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Royal United Hospital	Bath	Somerset
United Kingdom	Clatterbridge Centre for Oncology	Bebington	Wirral
United Kingdom	Centre for Cancer Research and Cell Biology at Queen's University Belfast	Belfast	Northern Ireland
United Kingdom	City Hospital (Birmingham)	Birmingham	England
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	West Midlands
United Kingdom	Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	Bradford Royal Infirmary	Bradford	West Yorkshire
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	Somerset
United Kingdom	Broomfield Hospital	Broomfield	Chelmsford
United Kingdom	Burnley General Hospital	Burnley	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	West Suffolk Hospital	Bury St. Edmunds	England
United Kingdom	Addenbrooke's Hospital	Cambridge	Cambridgeshire
United Kingdom	Kent and Canterbury Hospital	Canterbury	Kent
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Cumberland Infirmary	Carlisle	Cumbria
United Kingdom	Cheltenham General Hospital	Cheltenham	Gloucestershire
United Kingdom	Countess of Chester Hospital	Chester	Chesire
United Kingdom	Colchester General Hospital	Colchester
United Kingdom	Queen Alexandra Hospital	Cosham	Portsmouth
United Kingdom	Castle Hill Hospital	Cottingham	East Riding Of Yorkshire
United Kingdom	Mid Cheshire Hospitals Trust- Leighton Hopsital	Crewe	England
United Kingdom	Darlington Memorial	Darlington	England
United Kingdom	Derbyshire Royal Infirmary	Derby	England
United Kingdom	Doncaster Royal Infirmary	Doncaster	England
United Kingdom	Dorset County Hospital	Dorchester	Dorset
United Kingdom	Russells Hall Hospital	Dudley	England
United Kingdom	University Hospital of North Durham	Durham	England
United Kingdom	Eastbourne District General Hospital	Eastbourne	East Sussex
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Midlothian
United Kingdom	Royal Devon and Exeter Hospital	Exeter	Devon
United Kingdom	Royal Bolton Hospital	Farnworth	Bolton
United Kingdom	Beatson Institute for Cancer Research - Glasgow	Glasgow	Lanarkshire
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	Princess Alexandra Hospital	Harlow	Essex
United Kingdom	Hereford County Hospital	Hereford	England
United Kingdom	Wycombe General Hospital	High Wycombe	Buckinghamshire
United Kingdom	Huddersfield Royal Infirmary	Huddersfield	West Yorkshire
United Kingdom	Raigmore Hospital	Inverness	Highland
United Kingdom	Ipswich Hospital	Ipswich	Suffolk
United Kingdom	Kidderminster Hospital	Kidderminster	England
United Kingdom	Forth Valley Hospital	Larbert
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Glenfield Hospital	Leicester	England
United Kingdom	Lincoln Hospital	Lincoln
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	University Hospital Aintree	Liverpool	England
United Kingdom	Charing Cross Hospital	London	Greater London
United Kingdom	Guy's Hospital	London	England
United Kingdom	Helen Rollason Cancer Care Centre at North Middlesex Hospital	London	England
United Kingdom	Queen Elizabeth Hospital - Woolwich	London	Greater London
United Kingdom	St. Bartholomews Hospital	London	Greater London
United Kingdom	St. George's Hospital	London	Greater London
United Kingdom	St. Mary's Hospital	London	England
United Kingdom	UCL Cancer Institute	London	England
United Kingdom	University College of London Hospitals	London	England
United Kingdom	Mid Kent Oncology Centre at Maidstone Hospital	Maidstone	Kent
United Kingdom	Christie Hospital	Manchester	Greater Manchester
United Kingdom	Withington Hospital	Manchester	England
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate	Kent
United Kingdom	James Cook University Hospital	Middlesbrough	County Durham
United Kingdom	Freeman Hospital	Newcastle	Newcastle-upon-Tyne
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	Tyne & Wear
United Kingdom	St. Mary's Hospital	Newport	Isle Of Wight
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	Middlesex
United Kingdom	Nottingham City Hospital	Nottingham	Nottinghamshire
United Kingdom	Royal Oldham Hospital	Oldham	Greater Manchester
United Kingdom	Churchill Hospital	Oxford	Oxfordshire
United Kingdom	Poole Hospital	Poole	Dorset
United Kingdom	Rosemere Cancer Centre at Royal Preston Hospital	Preston	Lancashire
United Kingdom	Berkshire Cancer Centre at Royal Berkshire Hospital	Reading	Berkshire
United Kingdom	Queen's Hospital	Romford	Essex
United Kingdom	Conquest Hospital	Saint Leonards-on-Sea	East Sussex
United Kingdom	Scarborough General Hospital	Scarborough	North Yorkshire
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	South Yorkshire
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	England
United Kingdom	South Tyneside District Hospital	South Shields	Tyne & Wear
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United Kingdom	Southport and Formby District General Hospital	Southport	Merseyside
United Kingdom	Airedale General Hospital	Steeton	Keighley
United Kingdom	Lister Hospital	Stevenage	Hertfordshire
United Kingdom	Stepping Hill Hospital	Stockport	England
United Kingdom	North Tees Hospital	Stockton-on-Tees
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent	Staffordshire
United Kingdom	Sunderland Royal Hospital	Sunderland	England
United Kingdom	Royal Marsden - Sutton	Sutton	Surrey
United Kingdom	Good Hope Hospital	Sutton Coldfield	West Midlands
United Kingdom	King's Mill Hospital	Sutton-in-Ashfield	Nottinghamshire
United Kingdom	South West Wales Cancer Institute At Singleton Hospital	Swansea	Glamorgan
United Kingdom	Great Western Hospital	Swindon	Wiltshire
United Kingdom	Musgrove Park Hospital	Taunton	Somerset
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Warrington Hospital NHS Trust	Warrington	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	Essex
United Kingdom	Weston General Hospital	Weston Super Mare	Somerset
United Kingdom	West Cumberland Hospital	Whitehaven	England
United Kingdom	Royal Albert Edward Infirmary	Wigan	England
United Kingdom	New Cross Hospital	Wolverhampton
United Kingdom	Worcester Royal Hospital	Worcester	England
United Kingdom	Worthing Hospital	Worthing	England
United Kingdom	Yeovil District Hospital	Yeovil	Somerset

Sponsors (1)

Lead Sponsor	Collaborator
Medical Research Council

Countries where clinical trial is conducted

Switzerland,  United Kingdom, 

References & Publications (17)

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. — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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, Bo — View Citation

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. — View Citation

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. — View Citation

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 con — View Citation

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 — View Citation

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, — View Citation

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, Bah — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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, C — View Citation

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 — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Time to mortality	1:Not applicable
Secondary	Failure-free survival	Report of time from initiation of treatment to the first progression event of each patient	1:Not applicable
Secondary	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
Secondary	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
Secondary	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
Secondary	Skeletal related events	Reporting the incidence and types of skeletal related events	1:Not applicable
Secondary	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
Secondary	Progression-free survival	Reporting the incidence of mortality without a progression event	1:Not applicable
Secondary	Lymph node progression	Reporting the incidence and severity of lymph node events	1:Not applicable
Secondary	Distant metastases	Reporting the incidence and severity of distant metastatic events	1:Not applicable
Secondary	Treatment for progression	Identifying and reporting the treatments used in second line treatment. Incidence and types of treatments.	1:Not applicable
Secondary	Disease-specific survival	Reporting the mortality attributed to Prostate Cancer	1:Not applicable
Secondary	Non-prostate cancer death	Reporting the mortality not attributed to Prostate Cancer	1:Not applicable
Secondary	Metabolic effects	Reporting the incidence and severity of effects on metabolic systems	1:Not applicable

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