Official Title: “Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy [STAMPEDE] A 5-Stage Multi-Arm Randomized Controlled Trial”

RATIONALE: Androgens can cause the growth of prostate cancer cells. Androgen suppression may stop the adrenal glands from making androgens. Zoledronate may stop the growth of tumor cells in bone and help relieve some of the symptoms caused by bone metastases. It may also delay or prevent bone metastases in patients with nonmetastatic prostate cancer. Drugs used in chemotherapy, such as docetaxel and prednisolone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking the blood flow to the tumor. It is not yet known whether giving androgen suppression together with zoledronate, docetaxel, prednisolone, and/or celecoxib is more effective than giving androgen suppression alone in treating prostate cancer.

PURPOSE: This randomized phase II/III trial is studying how well giving androgen suppression together with zoledronate, docetaxel, prednisolone, and/or celecoxib works and compares it to androgen suppression alone in treating patients with locally advanced or metastatic prostate cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

OBJECTIVES:

Primary - 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. - 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 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

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

Primary:

• Overall survival at 4 years No

Secondary:

• Quality of life (QOL) by EORTC QOL Questionnaire C30 and prostate specific 25-item No
• Cost effectiveness by EuroQol No
• Failure-free survival No
• Toxicity Yes
• Skeletal related events No

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

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• 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

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

Lead Sponsor: Medical Research Council

Bristol Haematology and Oncology Centre

Bristol England BS2 8ED United Kingdom

Broomfield Hospital

Broomfield England CM1 7ET United Kingdom

Cancer Research Centre at Weston Park Hospital

Sheffield England S1O 2SJ United Kingdom

Castle Hill Hospital

Cottingham England HU16 5JQ United Kingdom

Christie Hospital

Manchester England M20 4BX United Kingdom

Churchill Hospital

Oxford England OX3 7LJ United Kingdom

Clatterbridge Centre for Oncology

Merseyside England CH63 4JY United Kingdom

Derbyshire Royal Infirmary

Derby England DE1 2QY United Kingdom

Great Western Hospital

Swindon England SN3 6BB United Kingdom

Guy's Hospital

London England SE1 9RT United Kingdom

Hereford Hospitals NHS Trust

Hereford England HR1 2ER United Kingdom

Huddersfield Royal Infirmary

Huddersfield, West Yorks England HD3 3EA United Kingdom

Ipswich Hospital

Ipswich England IP4 5PD United Kingdom

James Cook University Hospital

Middlesbrough England TS4 3BW United Kingdom

Leeds Cancer Centre at St. James's University Hospital

Leeds England LS9 7TF United Kingdom

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone England ME16 9QQ United Kingdom

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood England HA6 2RN United Kingdom

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham England B15 2TH United Kingdom

Queen's Hospital

Burton-upon-Trent England DE13 0RB United Kingdom

Royal Bournemouth Hospital NHS Trust

Bournemouth England BH7 7DW United Kingdom

Royal Devon and Exeter Hospital

Exeter England EX2 5DW United Kingdom

Royal Marsden - Surrey

Sutton England SM2 5PT United Kingdom

Royal Preston Hospital

Preston England PR2 9HT United Kingdom

Royal Shrewsbury Hospital

Shrewsbury England SY3 8XQ United Kingdom

Salford Royal Hospitals NHS Trust

Salford England M6 8HD United Kingdom

Southampton General Hospital

Southampton England SO16 6YD United Kingdom

Southend University Hospital NHS Foundation Trust

Westcliff-On-Sea England SS0 0RY United Kingdom

St. Luke's Cancer Centre at Royal Surrey County Hospital

Guildford England GU2 7XX United Kingdom

Stepping Hill Hospital

Stockport England SK2 7JE United Kingdom

Sunderland Royal Hospital

Sunderland England SR4 7TP United Kingdom

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton England BN2 5BE United Kingdom

Torbay Hospital

Torquay England TQ2 7AA United Kingdom

University College of London Hospitals

London England WIT 3AA United Kingdom

University Hospital of North Durham

Durham England DH1 5TW United Kingdom

Withington Hospital

Manchester England M20 8LR United Kingdom

Worthing Hospital

Worthing England BN11 2DH United Kingdom

Centre for Cancer Research and Cell Biology at Queen's University Belfast

Belfast Northern Ireland BT9 7BL United Kingdom

Beatson Institute for Cancer Research - Glasgow

Glasgow Scotland G61 1BD United Kingdom

Edinburgh Cancer Centre at Western General Hospital

Edinburgh Scotland EH4 2XU United Kingdom

South West Wales Cancer Institute

Swansea Wales SA2 8QA United Kingdom

Velindre Cancer Center at Velindre Hospital

Cardiff Wales CF14 2TL United Kingdom

Overall Clinical Trial Officials and Contacts

Nicholas D. James, MD Study Chair University Hospital Birmingham  

Information obtained from ClinicalTrials.gov on July 23, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00268476

Study ID Number: CDR0000455008

ClinicalTrials.gov Identifier: NCT00268476

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database