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
Francesca Schiavone
+44 (0)20 7670 4632
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 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 treatment) slows the growth of prostate cancers. This type of treatment is called hormone treatment and is often used when prostate cancers have spread outside of 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.

There are increasing numbers of treatments available for advanced 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, which is called STAMPEDE, is to assess five of these treatments, given earlier in the course of the disease in combination with hormone treatment.

The treatments assessed during the trial 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, Docetaxel is currently being used to treat a range of cancers including lung, breast and ovarian cancer as well as prostate cancer. Docetaxel is already known to prolong survival in men with relapsed metastatic prostate cancer.

3. Celecoxib: An aspirin-like drug that is used to treat arthritis. Celecoxib 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 pre-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. This agent is given along with prednisolone and is already known to prolong survival when given to men following failure of docetaxel chemotherapy.

5. Prostate radiotherapy (included from protocol version 9.0): Treatment with high-energy x-rays targeted to the prostate gland. This treatment is now mandatory for patients with cancer that is confined to the prostate gland as large trials have shown it improves survival times. We are interested in whether we should give radiotherapy to the prostate if the cancer has already spread.

6. Enzalutamide (included from protocol version 12.0): This is a blocker of androgen receptors. These stimulate the cancer when hormone therapies have failed. Enzalutamide may be mutually complementary to abiraterone in terms of blocking mechanisms of resistance. 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 treatments described above with hormone treatment. A computer program will be used to allocate which treatment the patient receives, using a chance process. 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. More than 8,000 patients will join the trial with answers becoming available over 7 to 12 years.
Research Details
  • OBJECTIVES:

    Primary

    - Compare the safety of Androgen Deprivation Therapy (ADT) alone vs ADT in varying combinations with enzalutamide and abiraterone and/or radiotherapy to the prostate (and previously celecoxib, zoledronic acid, docetaxel and abiraterone alone) 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 currently randomised to 1 of 3 treatment arms (A, H and J). The other arms are now closed to recruitment.

    - Arm A (Androgen Deprivation Therapy [ADT] (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 (ADT and zoledronic acid): Patients undergo ADT (+/- RT) as in arm A. 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 (no longer recruiting).

    - Arm C (ADT, docetaxel, and prednisolone): Patients undergo ADT (+/- RT) as in arm A. 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 (no longer recruiting).

    - Arm D (ADT and celecoxib): Patients undergo ADT as in arm A. Patients also receive oral celecoxib twice daily for 1 year in the absence of disease progression or unacceptable toxicity (no longer recruiting).

    - Arm E (ADT, zoledronic acid, docetaxel, and prednisolone): Patients undergo ADT (+/- RT) as in arm A. Patients also receive zoledronic acid as in arm B and docetaxel and prednisolone as in arm C (no longer recruiting)..

    - Arm F (ADT, zoledronic acid, and celecoxib): Patients undergo ADT as in arm A. Patients also receive zoledronic acid as in arm B and celecoxib as in arm D (no longer recruiting).

    - Arm G (ADT and abiraterone): Patients undergo ADT (+/- RT) as in arm A. Patients also receive oral abiraterone once daily together with prednisolone or prednisone 5mg daily to prevent secondary ACTH excess (no longer recruiting).

    - Arm H (ADT and radiotherapy to the prostate): Patients (newly-diagnosed-metastatic only) undergo ADT, as in arm A. Patients also receive radiotherapy to the prostate. Two radiotherapy dose-fractionation schedules are permitted. In either case, radiotherapy is prescribed such that at least 95% of the PTV receives the prescribed dose:

    36Gy in 6 fractions of 6Gy, administered weekly over 6 consecutive weeks or 55Gy in 20 fractions of 2.75Gy, administered daily, five days per week, over 4 consecutive weeks.

    - Arm J (ADT, enzalutamide and abiraterone): Patients undergo ADT, as in arm A. Patients also receive oral enzalutamide once daily and abiraterone once daily together with prednisolone or prednisone 5mg daily to prevent secondary ACTH excess.

    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, Astellas. Core funding: Medical Research Council PROJECTED ACCRUAL: Approximately 5000 patients will be accrued for this 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

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)

Intervention Type
See Interventions above
Primary Outcome Measures
    Overall survival; null
Secondary Outcome Measures
    Failure-free survival; null; Cost effectiveness by EuroQol; null; Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item; null; Toxicity; null; Skeletal related events; null
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 - N/A
Who Can Participate
Patients
Number of Participants
8100
Participant Inclusion Criteria
    HIGH-RISK NEWLY DIAGNOSED NON-METASTATIC NODE-NEGATIVE DISEASE

    Both:

    At least two of:

    - Stage 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 sought in advance of consent, after discussion with MRC CTU)

    OR NEWLY DIAGNOSED METASTATIC OR NODE-POSITIVE DISEASE

    At least one of:

    - Stage Tany N+ M0

    - Stage Tany Nany M+

    OR PREVIOUSLY TREATED WITH RADICAL SURGERY AND/OR RADIOTHERAPY, NOW RELAPSING1

    At least one of:

    - PSA ≥4ng/ml and rising with doubling time less than 6 months

    - PSA ≥20ng/ml

    - N+

    - M+

    AND FOR ALL PATIENTS I. Histologically confirmed prostate adenocarcinoma

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

    III. Fit for all protocol treatment2 and follow-up, WHO performance status 0-23

    IV. Have completed the appropriate investigations prior to randomisation

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

    VI. Estimated creatinine clearance >30ml/min

    VII. Serum potassium ≥3.5mmol/L

    VIII. Written informed consent

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

    X. Using effective contraceptive method if applicable

    PATIENT EXCLUSION CRITERIA Patients must not fulfil any of the criteria, below. I. Prior systemic therapy for locally advanced or metastatic prostate cancer except as listed in Section 4.1.3

    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 physician, is likely to interfere with STAMPEDE treatment or assessment

    V. Patients with contra-indications to prednisolone, including active peptic ulceration or a history of gastrointestinal bleeding

    VI. Patients with active inflammatory bowel disease

    VII. Symptomatic peripheral neuropathy grade (NCI CTC)

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

    IX. 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)

    - Cerebrovascular disease (e.g. stroke or transient ischaemic episode) less than 2 years prior to randomisation

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

    X. Patients receiving treatment with drugs known to induce CYP3A4 (including phenytoin, carbamazepine, Phenobarbital)

    XI. Prior exposure to abiraterone

    XII. Prior exposure to enzalutamide

    XIII. Prior chemotherapy for prostate cancer

    XIV. Prior therapy with zoledronic acid or other bisphosphonates other than treatment for hypercalcaemia or low bone density

    XV. Prior exposure to policy of long-term hormone therapy before randomisation (unless as described in Section 4.4.2)

    XVI. History of seizure including any febrile seizure, loss of consciousness, or transient ischaemic attack within 12 months of randomisation or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization)

    XVII. Unexplained history of loss of consciousness within 12 months of randomisation

    XVIII. Operation of heavy machinery during treatment

    SELECTION CRITERIA FOR COMPARISON OF RESEARCH (M1) RT FOR METASTATIC DISEASE

    All patients meeting criteria in Section 4.1 and 4.2 are eligible for the trial, but not all can be allocated to the research (M1) radiotherapy arm. The selection criteria for this "RT to the prostate" comparison are:

    - Newly-diagnosed prostate cancer

    - Demonstrable M1 disease

    - No contraindication to radiotherapy e.g. no previous pelvic radiotherapy and no history of inflammatory bowel disease

    - No previous radical prostatectomy

    Any patients meeting these criteria will have a chance to be allocated to Arm H.
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
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
Stoke Mandeville Hospital
Aylesbury
England
HP21 8AL
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
William Harvey Hospital
Willesborough
England
TN24 0LZ
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
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
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
Kidderminster Hospital
Kidderminster
England
Royal Albert Edward Infirmary
Lancanshire
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
Trial Contact(s)
Primary Trial Contact
Francesca Schiavone
+44 (0)20 7670 4632
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 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 2017

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

20 Dec 2005

Date updated in source

24 Jul 2014