Clinical Trial Name - Androgen Suppression Alone or Combined With Zoledronate, Docetaxel, Prednisolone, and/or Celecoxib

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.

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.