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ACTIVE NOT RECRUITING

NCT00268476

PHASE2/PHASE3

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

Sponsor: Medical Research Council

View on ClinicalTrials.gov

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.

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

Key Details

Gender

MALE

Age Range

Any - 120 Years

Study Type

INTERVENTIONAL

Enrollment

11992

Start Date

2005-07-08

Completion Date

2030-12

Last Updated

2023-04-18

Healthy Volunteers

Conditions

Prostate Cancer

Interventions

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

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

Locations (120)

Lausanne Centre Hospitalier Universitaire

Lausanne, Canton of Vaud, Switzerland

Winterthur Hospital

Winterthur, Canton of Zurich, Switzerland

Kantonsspital Graubuenden

Chur, Kanton Graubünden, Switzerland

Hirslanden Klinik Aarau

Aarau, Switzerland

Universitaetsspital-Basel

Basel, Switzerland

Inselspital Bern

Bern, Switzerland

Liestal Hospital

Liestal, Switzerland

Kantonsspital - St. Gallen

Sankt Gallen, Switzerland

UniversitaetsSpital Zuerich

Zurich, Switzerland

City Hospital Triemli

Zurich, Switzerland

Berkshire Cancer Centre at Royal Berkshire Hospital

Reading, Berkshire, United Kingdom

Royal Bolton Hospital

Farnworth, Bolton, United Kingdom

Wycombe General Hospital

High Wycombe, Buckinghamshire, United Kingdom

Addenbrooke's Hospital

Cambridge, Cambridgeshire, United Kingdom

Broomfield Hospital

Broomfield, Chelmsford, United Kingdom

Countess of Chester Hospital

Chester, Chesire, United Kingdom

James Cook University Hospital

Middlesbrough, County Durham, United Kingdom

Cumberland Infirmary

Carlisle, Cumbria, United Kingdom

North Devon District Hospital

Barnstaple, Devon, United Kingdom

Royal Devon and Exeter Hospital

Exeter, Devon, United Kingdom

Royal Bournemouth Hospital

Bournemouth, Dorset, United Kingdom

Dorset County Hospital

Dorchester, Dorset, United Kingdom

Poole Hospital

Poole, Dorset, United Kingdom

Castle Hill Hospital

Cottingham, East Riding Of Yorkshire, United Kingdom

Eastbourne District General Hospital

Eastbourne, East Sussex, United Kingdom

Conquest Hospital

Saint Leonards-on-Sea, East Sussex, United Kingdom

William Harvey Hospital

Ashford, England, United Kingdom

Stoke Mandeville Hospital

Aylesbury, England, United Kingdom

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, England, United Kingdom

City Hospital (Birmingham)

Birmingham, England, United Kingdom

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, United Kingdom

Burnley General Hospital

Burnley, England, United Kingdom

Queen's Hospital

Burton-on-Trent, England, United Kingdom

West Suffolk Hospital

Bury St Edmunds, England, 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

Russells Hall Hospital

Dudley, England, United Kingdom

University Hospital of North Durham

Durham, England, United Kingdom

Gloucestershire Royal Hospital

Gloucester, England, United Kingdom

Hereford County Hospital

Hereford, England, United Kingdom

Kidderminster Hospital

Kidderminster, England, United Kingdom

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Glenfield Hospital

Leicester, England, United Kingdom

Royal Liverpool University Hospital

Liverpool, England, United Kingdom

University Hospital Aintree

Liverpool, England, United Kingdom

Helen Rollason Cancer Care Centre at North Middlesex Hospital