Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

Prostate cancers depend upon the male hormone testosterone for their growth. Lowering testosterone levels (either by removing all or part of both testes, or by giving anti-hormone injections) slows the growth of prostate cancers. This is called hormone treatment and is often used when prostate cancers have spread outside the prostate gland. Although hormone treatment is usually successful at stopping the cancer growing for a period of time, the cancer will begin to grow again in most men.

A number of newer treatments have recently become available for prostate cancer. These treatments are usually used in prostate cancer when hormone treatment is no longer effective and the cancer has started to grow again. The aim of this trial is to assess four of these newer treatments, given earlier in the course of the disease in combination with hormone treatment.

The treatments assessed are:

1. Zoledronic acid: Prostate cancer cells can spread to bones and weaken them. Zoledronic acid is a drug that reduces bone destruction and hardens bones. This may make them more resistant to attack by cancer cells.

2. Docetaxel: A drug that stops cells replicating that is currently being used to treat lung, breast and ovarian cancer.

3. Celecoxib: An aspirin-like drug that is used to treat arthritis. It slows down the growth of cancer cells in the laboratory. We wished to see if it had the same effect on cancer cells in patients. Recruitment to new patients for the evaluation of this drug is finished as a planned interim analysis failed to demonstrate sufficient activity.

4. Abiraterone (included from protocol version 8.0): An inhibitor of steroid hormone synthesis that blocks prostate cancer cells from generating their own male hormones. This is thought to be a major way in which prostate cancer cells resume growth following castration based therapies. The agent prolongs survival when given to men following failure of docetaxel chemotherapy.

STAMPEDE will look at the effect of combining one or two of the new treatments described above with hormone treatment. The trial will look at the effects of the combined treatments on quality of life and find out whether the new treatment combinations increase the time when the cancer is not growing and ultimately results in patients living longer. The study will also look at which treatment provides the greater value for money for the health service. Around 4000 men will join the trial with answers becoming available over 7-12 years.

Further Study Information

OBJECTIVES:

Primary

• Compare the safety of androgen suppression (AS) alone vs AS in varying combinations with zoledronic acid, docetaxel,,abiraterone (and previously celecoxib) in patients with locally advanced or metastatic prostate cancer.

• Compare failure-free survival and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter, pilot study. Patients are randomized to 1 of 5 treatment arms.

• Arm A (androgen suppression [AS] (plus RT for newly-diagnosed non-metastatic disease) [control]): Patients undergo bilateral orchidectomy or receive luteinizing hormone-releasing hormone (LHRH) analogues to achieve castration levels of testosterone.

• Arm B (AS and zoledronic acid): Patients undergo AS (+/- RT) as in arm I. Patients also receive zoledronic acid IV over 15 minutes on day 1. Treatment repeats every 3 weeks for 6 courses and then every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

• Arm C (AS, docetaxel, and prednisolone): Patients undergo AS (+/- RT) as in arm I. Patients also receive docetaxel IV over 1 hour on day 1 and oral prednisolone twice daily on days 1-21. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm E (AS, zoledronic acid, docetaxel, and prednisolone): Patients undergo AS (+/- RT) as in arm I. Patients also receive zoledronic acid as in arm II and docetaxel and prednisolone as in arm III.

• Arm G (AS and abiraterone): Patients undergo AS (+/- RT) as in arm I. Patients also receive oral abiraterone once daily together with prednisolone or prednisone 5mg daily to prevent secondary ACTH excess.

No longer recruiting:

• Arm D (AS and celecoxib): Patients undergo AS as in arm I. Patients also receive oral celecoxib twice daily for 1 year in the absence of disease progression or unacceptable toxicity.

• Arm F (AS, zoledronic acid, and celecoxib): Patients undergo AS as in arm I. Patients also receive zoledronic acid as in arm II and celecoxib as in arm IV.

After completion of study treatment, patients are followed periodically thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK. Grant funding: Novartis, Sanofi-Aventis, Pfizer, Janssen. Core funding: Medical Research Council

PROJECTED ACCRUAL: Approximately 4000 patients will be accrued for this study.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of locally advanced or metastatic adenocarcinoma of the prostate, meeting 1 of the following criteria:

HIGH-RISK NEWLY DIAGNOSED NON-METASTATIC NODE-NEGATIVE DISEASE (i) At least two of: Stage T3/4, PSA≥40ng/ml or Gleason sum score 8-10 (ii) Intention to treat with radical radiotherapy (unless there is a contra-indication; exemption can sought in advance of consent, after discussion with MRC CTU)

OR

NEWLY DIAGNOSED METASTATIC OR NODE-POSITIVE DISEASE

(i) Stage Tany N+ M0 or Tany Nany M+ (See Note 1)

OR

PREVIOUSLY TREATED WITH RADICAL SURGERY OR RADIOTHERAPY, NOW RELAPSING (See Note 2)

At least one of:

(i) PSA ≥4ng/ml and rising with doubling time less than 6 months (ii) PSA ≥20ng/ml (iii) N+ (iv) M+

1. Note: From version 8.0, patients with multiple sclerotic bone metastases with PSA≥100ng/ml must have histological confirmation

2. Note: Prior hormone therapy for localised disease must have been completed at least 12 months previously and have been no longer than 12 months in duration. It can have been given as adjuvant or neoadjuvant therapy.

• No prior systemic therapy for locally advanced or metastatic prostate cancer

• No other concurrent cyclooxygenase-2 inhibitors

• No concurrent participation in another clinical trial for prostate cancer

INCLUSION CRITERIA FOR FOR ALL PATIENTS

• Histologically confirmed prostate adenocarcinoma

• Intention to treat with long-term hormone therapy

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

• Have completed the appropriate investigations prior to randomisation

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

• Estimated creatinine clearance >30ml/min

• Serum potassium ≥3.5mmol/L

• Written informed consent

• Willing and expected to comply with follow-up schedule

• Using effective contraceptive method if applicable

PATIENT EXCLUSION CRITERIA Patients must not fulfil any of the criteria, below.

• Prior systemic therapy for locally advanced or metastatic prostate cancer except as listed in listed in Section 4.1.3 of the protocol

• Metastatic brain disease or leptomeningeal disease

• 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 51.3Rmol/l or 3mg/dl)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 x ULN

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

• Patients with active peptic ulceration, gastrointestinal bleeding, inflammatory bowel disease

• Symptomatic peripheral neuropathy grade 2 (NCI CTC)4

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

• Patients with confirmed severe cardiovascular history e.g.:

1. Severe/unstable angina

2. Myocardial infarction

3. Severe cardiac failure (NYHA II-IV5)

4. Cerebrovascular disease (e.g. stroke or transient ischaemic episode)

5. Patients with uncontrolled hypertension defined as systolic BP ≥160 mmHg or diastolic BP ≥95 mmHg).

• Patients who have been scheduled to have major dental extractions within the next 2 years

• Patients receiving treatment with drugs known to induce CYP3A4 (including phenytoin, carbamazepine, Phenobarbital). A full list is included in Appendix G.

• Prior exposure to abiraterone

• Prior chemotherapy for prostate cancer

• Prior therapy with zoledronic acid other than short-term treatment for hypercalcaemia.

Trial Contact Information

Trial Lead Organizations/Sponsors

Medical Research Council's Working Party on Leukemia in Adults and Children

Nicholas D. James

Study Chair

Charlene Green		Ph: +44 (0)20 7670 4882
		Email: stampede@ctu.mrc.ac.uk

Switzerland
	Aarau
	Hirslanden Klinik Aarau
	Basel
	Universitaetsspital-Basel
	Bern
	Inselspital Bern
	Chur
	Kantonsspital Graubuenden
	St. Gallen
	Kantonsspital - St. Gallen
	Zurich
	City Hospital Triemli
	UniversitaetsSpital Zuerich
United Kingdom
	Belfast
	Centre for Cancer Research and Cell Biology at Queen's University Belfast
	Newport
	St. Mary's Hospital
England
	Ashford-Kent
	William Harvey Hospital
		Contact Person	Ph: 44-1233-633-331
	Aylesbury-Buckinghamshire
	Stoke Mandeville Hospital
	Barnstaple
	North Devon District Hospital
	Basingstoke
	Basingstoke and North Hampshire NHS Foundation Trust
	Bath
	Royal United Hospital
	Birmingham
	City Hospital (Birmingham)
	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
	Bournemouth
	Royal Bournemouth Hospital
	Bradford
	Bradford Royal Infirmary
	Brighton
	Sussex Cancer Centre at Royal Sussex County Hospital
	Bristol
	Bristol Haematology and Oncology Centre
	Broomfield
	Broomfield Hospital
	Burnley
	Burnley General Hospital
	Burton-upon-Trent
	Queen's Hospital
	Bury St. Edmunds
	West Suffolk Hospital
	Canterbury
	Kent and Canterbury Hospital
	Carlisle
	Cumberland Infirmary
	Cheltenham
	Cheltenham General Hospital
	Chester
	Countess of Chester Hospital
	Cosham
	Queen Alexandra Hospital
	Cottingham
	Castle Hill Hospital
	Crewe
	Mid Cheshire Hospitals Trust- Leighton Hopsital
	Darlington
	Darlington Memorial
	Derby
	Derbyshire Royal Infirmary
	Doncaster
	Doncaster Royal Infirmary
	Dorchester
	Dorset County Hospital
	Dudley
	Russells Hall Hospital
	Durham
	University Hospital of North Durham
	Eastbourne
	Eastbourne District General Hospital
	Essex
	Princess Alexandra Hospital
	Exeter
	Royal Devon and Exeter Hospital
	Farnworth
	Royal Bolton Hospital
	Gloucester
	Gloucestershire Royal Hospital
	Guildford
	St. Luke's Cancer Centre at Royal Surrey County Hospital
	Hereford
	Hereford Hospitals
	High Wycombe
	Wycombe General Hospital
	Huddersfield, West Yorks
	Huddersfield Royal Infirmary
	Ipswich
	Ipswich Hospital
	Keighley
	Airedale General Hospital
	Kidderminster Worcestershire
	Kidderminster Hospital
	Lancanshire
	Royal Albert Edward Infirmary
	Leeds
	Leeds Cancer Centre at St. James's University Hospital
	Leicester
	Glenfield Hospital
	Liverpool
	Royal Liverpool University Hospital
	University Hospital Aintree
	London
	Charing Cross Hospital
	Guy's Hospital
	Helen Rollason Cancer Care Centre at North Middlesex Hospital
	Queen Elizabeth Hospital - Woolwich
	St. George's Hospital
	St. Mary's Hospital
	UCL Cancer Institute
	University College of London Hospitals
	Maidstone
	Mid Kent Oncology Centre at Maidstone Hospital
	Manchester
	Christie Hospital
	Withington Hospital
	Margate
	Queen Elizabeth The Queen Mother Hospital
	Merseyside
	Clatterbridge Centre for Oncology
	Middlesbrough
	James Cook University Hospital
	Newcastle-Upon-Tyne
	Northern Centre for Cancer Treatment at Newcastle General Hospital
	Northwood
	Mount Vernon Cancer Centre at Mount Vernon Hospital
	Nottingham
	Nottingham City Hospital
	Oldham
	Royal Oldham Hospital
	Oxford
	Churchill Hospital
	Poole Dorset
	Dorset Cancer Centre
	Preston
	Rosemere Cancer Centre at Royal Preston Hospital
	Reading
	Berkshire Cancer Centre at Royal Berkshire Hospital
	Romford
	Queen's Hospital
	Saint Leonards-on-Sea
	Conquest Hospital
	Salford
	Hope Hospital
	Scarborough
	Scarborough General Hospital
	Sheffield
	Cancer Research Centre at Weston Park Hospital
	Shrewsbury
	Royal Shrewsbury Hospital
	South Shields
	South Tyneside District Hospital
	Southampton
	Southampton General Hospital
	Southport
	Southport and Formby District General Hospital
	Stevenage
	Lister Hospital
	Stockport
	Stepping Hill Hospital
	Stoke-on-Trent
	University Hospital of North Staffordshire (City General Hospital)
	Sunderland
	Sunderland Royal Hospital
	Sutton
	Royal Marsden - Surrey
	Sutton-in-Ashfield
	King's Mill Hospital
	Swindon
	Great Western Hospital
	Taunton
	Musgrove Park Hospital
	Torquay
	Torbay Hospital
	Warrington
	Warrington Hospital NHS Trust
	Westcliff-On-Sea
	Southend University Hospital NHS Foundation Trust
	Weston Super Mare
	Weston General Hospital
	Whitehaven
	West Cumberland Hospital
	Worcester
	Worcester Royal Hospital
	Worthing
	Worthing Hospital
Scotland
	Ayr
	Ayr Hospital
	Edinburgh
	Edinburgh Cancer Centre at Western General Hospital
	Glasgow
	Beatson Institute for Cancer Research - Glasgow
	Inverness
	Raigmore Hospital
Wales
	Aberystwyth
	Bronglais General Hospital
	Cardiff
	Velindre Cancer Center at Velindre Hospital
	Swansea
	South West Wales Cancer Institute

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00268476
Information obtained from ClinicalTrials.gov on March 12, 2012

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