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.

Intervention(s) in this Clinical Trial

• Drug: celecoxib
• Drug: docetaxel
• Drug: prednisolone
• Drug: releasing hormone agonist therapy
• Drug: zoledronic acid
• Procedure: orchiectomy

Primary Measures

• Overall survival at 4 years
  • Safety Issue?: No

Secondary Measures

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Medical Research Council

Overall Clinical Trial Officials and Contacts

Nicholas D. James, MD Study Chair University Hospital Birmingham  

Information obtained from ClinicalTrials.gov on July 02, 2009

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