Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Androgen Suppression Alone or Combined With Zoledronate, Docetaxel, Prednisolone, and/or Celecoxib in Treating Patients With Locally Advanced or Metastatic Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Active	Not specified	Other	MRC-STAMPEDE EU-205102, MRC-PR08, ISRCTN78818544, EUDRACT-2004-000193-31, NCT00268476

Objectives

Primary

1. Compare the safety of androgen suppression (AS) alone vs AS in varying combinations with zoledronate, docetaxel, prednisolone, and celecoxib in patients with locally advanced or metastatic prostate cancer.
2. Compare failure-free survival and overall survival of patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Diagnosis of locally advanced or metastatic adenocarcinoma of the prostate, meeting 1 of the following criteria:
  • High risk newly diagnosed disease, meeting 1 of the following criteria:
    • Histologically confirmed T3-4, N0, M0 disease with prostate-specific antigen (PSA) ≥ 40 ng/mL or Gleason sum score 8-10
    • Histologically confirmed disease with any T, N+, M0 OR any T, any N, M+
    • Multiple sclerotic bone metastases with a PSA ≥ 100 ng/mL without histological confirmation
  • Histologically confirmed previously treated disease with radical surgery or radiotherapy that is now relapsing AND meets 1 of the following criteria:
    • PSA ≥ 4 ng/mL and rising with doubling time less than 6 months
    • PSA ≥ 20 ng/mL



• Intention to treat with long-term androgen suppression



• Testosterone normal (prior to the start of hormonal therapy)



• No metastatic brain disease or leptomeningeal disease

Prior/Concurrent Therapy:

• See Disease Characteristics
• Prior adjuvant or neoadjuvant hormonal therapy for localized disease must have been completed at least 12 months ago and have been no longer than 12 months in duration
• No prior cyclooxygenase-2 inhibitor therapy that lasted ≥ 6 months prior to study entry
• No surgery (e.g., transurethral resection of the prostate [TURP]) performed within the past 4 weeks
• 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

Patient Characteristics:

• WHO performance status 0-2
• Neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• ALT or AST ≤ 1.5 times upper limit of normal (ULN)
• Bilirubin normal
• Serum creatinine ≤ 1.5 times ULN
• No renal insufficiency with estimated creatinine clearance < 30 mL/min
• No severe congestive heart failure
• No history of severe/unstable angina
• No history of myocardial infarction
• No history of New York Heart Association class II-IV severe cardiac failure
• No history of cerebrovascular disease (e.g., stroke or transient ischemic episode)
• No symptomatic peripheral neuropathy ≥ grade 2
• No active peptic ulceration, gastrointestinal bleeding, or inflammatory bowel disease
• No other previous or current malignant disease which, in the judgement of the responsible physician, is likely to interfere with study treatment or assessment
• Willing and expected to comply with follow-up schedule

Expected Enrollment

Approximately 3,300 patients will be accrued for this study.

Outcomes

Overall survival at 4 years

Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item
Cost effectiveness by EuroQol
Failure-free survival
Toxicity
Skeletal related events

Outline

This is a randomized, controlled, multicenter, pilot study. Patients are randomized to 1 of 6 treatment arms.

• Arm I (androgen suppression [AS] only [control]): Patients undergo bilateral orchidectomy or receive luteinizing hormone-releasing hormone (LHRH) analogues to achieve castration levels of testosterone.



• Arm II (AS and zoledronate): Patients undergo AS as in arm I. Patients also receive zoledronate 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 III (AS, docetaxel, and prednisolone): Patients undergo AS 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 IV (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 V (AS, zoledronate, docetaxel, and prednisolone): Patients undergo AS as in arm I. Patients also receive zoledronate as in arm II and docetaxel and prednisolone as in arm III.



• Arm VI (AS, zoledronate, and celecoxib): Patients undergo AS as in arm I. Patients also receive zoledronate 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

Trial Contact Information

Trial Lead Organizations

Medical Research Council Clinical Trials Unit

Nicholas James, MD, Protocol chair		Ph: 44-121-697-8314 Email: n.d.james@bham.ac.uk

United Kingdom
England
	Birmingham
	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
		Nicholas James, MD	Ph:  44-121-697-8314
			Email: n.d.james@bham.ac.uk
	Bournemouth
	Royal Bournemouth Hospital NHS Trust
		Contact Person	Ph:  44-202-303-626
	Brighton
	Sussex Cancer Centre at Royal Sussex County Hospital
		Angus Robinson	Ph:  44-127-369-6955
			Email: angus.robinson@bsuh.nhs.uk
	Bristol
	Bristol Haematology and Oncology Centre
		Amit Bahl, MD	Ph:  44-117-928-2468
			Email: amit.bahl@ubht.nhs.uk
	Broomfield
	Broomfield Hospital
		Priscilla Leone, MD	Ph:  44-1245-516-318
			Email: enca.parsons@meht.nhs.uk
	Burton-upon-Trent
	Queen's Hospital
		Contact Person	Ph:  44-1708-435-440
	Cottingham
	Castle Hill Hospital
		J.W. Hetherington, MD	Ph:  44-1482-622183
			Email: jwhurologist@yahoo.co.uk
	Derby
	Derbyshire Royal Infirmary
		Prabir Chakraborti, MD	Ph:  44-1322-347-141
			Email: prabir.chakraborti@derbyhospitals.nhs.uk
	Durham
	University Hospital of North Durham
		Rhona McMenemin	Ph:  44-191-256-3579
	Exeter
	Royal Devon and Exeter Hospital
		Denise Sheehan, MD	Ph:  44-1392-402-114
	Guildford
	St. Luke's Cancer Centre at Royal Surrey County Hospital
		Robert Laing, MD	Ph:  44-1483-571-112
			Email: rlaing@royalsurrey.nhs.uk
	Hereford
	Hereford Hospitals NHS Trust
		Audrey Cook, MD	Ph:  44-8454-222-871
	Huddersfield, West Yorks
	Huddersfield Royal Infirmary
		Contact Person	Ph:  44-1484-342-999
	Ipswich
	Ipswich Hospital
		Contact Person	Ph:  44-1473-702-572
	Leeds
	Leeds Cancer Centre at St. James's University Hospital
		Peter Whelan, MD	Ph:  44-113-206-4904
			Email: peter.whelan@leedsth.nhs.uk
	London
	Guy's Hospital
		Rick Popert, MD	Ph:  44-20-7188-6794
			Email: rick.popert@gsst.nhs.uk
	University College of London Hospitals
		Stephen Harland, MD	Ph:  44-207-380-9287
			Email: stephen.harland@uclh.nhs.uk
	Maidstone
	Mid Kent Oncology Centre at Maidstone Hospital
		Sharon Beelsey	Ph:  44-1622-225074
			Email: sbeesley@nhs.net
	Manchester
	Christie Hospital
		Noel Clarke	Ph:  44-161-446-3364
	Withington Hospital
		Vijay Sangar, MD	Ph:  44-161-217-4290
	Merseyside
	Clatterbridge Centre for Oncology
		Contact Person	Ph:  44-151-334-1155
	Middlesbrough
	James Cook University Hospital
		John Hardman	Ph:  44-1642-853-285
			Email: john.hardman@stees.nhs.uk
	Northwood
	Mount Vernon Cancer Centre at Mount Vernon Hospital
		Peter Hoskin, MD	Ph:  44-1923-844-533
			Email: peterhoskin@nhs.net
	Oxford
	Churchill Hospital
		Andrew Protheroe, MD	Ph:  44-1865- 226-183
			Email: samantha.knipe@cancer.org.uk
	Preston
	Royal Preston Hospital
		Alison Birtle, MD	Ph:  44-1772-522-752
			Email: alison.birtle@lthtr.nhs.uk
	Salford
	Hope Hospital
		Noel Clarke	Ph:  44-161-206-5568
	Sheffield
	Cancer Research Centre at Weston Park Hospital
		Catherine Ferguson, MD	Ph:  44-114-226-5077
	Shrewsbury
	Royal Shrewsbury Hospital
		Narayanan Srihari, MD	Ph:  44-1743-261656
	Southampton
	Southampton General Hospital
		Catherine Heath	Ph:  44-23-8079-4202
	Stockport
	Stepping Hill Hospital
		Contact Person	Ph:  44-161-419-5883
	Sunderland
	Sunderland Royal Hospital
		Ian Pedley	Ph:  44-191-256-3575
	Sutton
	Royal Marsden - Surrey
		David P. Dearnaley, MD, FRCP, FRCR	Ph:  44-20-8661-3271
	Swindon
	Great Western Hospital
		David Cole, MD	Ph:  44-1793-604-336
	Torquay
	Torbay Hospital
		Anna Lydon, MD	Ph:  44-1803-655-376
	Westcliff-On-Sea
	Southend University Hospital NHS Foundation Trust
		David Tsang, MD	Ph:  44-1902-435-555
	Worthing
	Worthing Hospital
		Contact Person	Ph:  44-1903-205-111 ext. 4225
Northern Ireland
	Belfast
	Centre for Cancer Research and Cell Biology at Queen's University Belfast
		Joe O'Sullivan	Ph:  44-28-9069-9204
			Email: joe.osullivan@qub.ack.uk
Scotland
	Edinburgh
	Edinburgh Cancer Centre at Western General Hospital
		Duncan McLaren	Ph:  44-131-537-3269
			Email: duncan.mclaren@luht.scot.nhs.uk
	Glasgow
	Beatson Institute for Cancer Research - Glasgow
		Contact Person	Ph:  44-141-211-6369
Wales
	Cardiff
	Velindre Cancer Center at Velindre Hospital
		Malcolm Mason, MD	Ph:  44-29-2031-6964
			Email: masonmd@cardiff.ac.uk
	Swansea
	South West Wales Cancer Institute
		Gianfilippo Bertelli, MD, FRCPE	Ph:  44-179-228-5826
			Email: gianfilippo.bertelli@swansea-tr.wales.nhs.uk

Registry Information
Official Title		Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy [STAMPEDE] A 5-Stage Multi-Arm Randomized Controlled Trial
Trial Start Date		2005-09-19
Registered in ClinicalTrials.gov		NCT00268476
Date Submitted to PDQ		2005-09-29
Information Last Verified		2008-03-30