Clinical trial NCT00079001
Conditions: Metastatic Cancer Prostate Cancer
Keywords: adenocarcinoma of the prostate recurrent prostate cancer stage IV prostate cancer bone metastases
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2004-01-01; Completion date: 2014-10-01
Enrollment: 645 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Zoledronate may prevent or decrease skeletal (bone)-related events (such as pain or fractures) caused by bone metastases and androgen deprivation therapy. It is not yet known whether treatment with zoledronate is effective in preventing bone-related events in patients who have prostate cancer and bone metastases.

PURPOSE: This randomized phase III trial is studying how well zoledronate works in preventing bone-related events in patients who are receiving androgen deprivation therapy for prostate cancer and bone metastases.

Detailed description:
Zoledronic acid decreases the risk of skeletal related events in men with prostate cancer metastatic to bone and disease progression after primary hormonal therapy.

This study is designed to evaluate whether earlier treatment with zoledronic acid will further decrease the risk of skeletal related events. This is a randomized, double-blind, placebo-controlled, multicenter study followed by an open-label study. Patients are stratified according to ECOG performance status (0-1 vs 2), prior skeletal-related event (no vs yes), and serum alkaline phosphatase (\< upper limit of normal \[ULN\] vs ≥ ULN).

The primary objective of the study is to determine whether treatment with zoledronic acid at the time of initiation of androgen deprivation therapy for metastatic prostate cancer will delay the time to first skeletal related event. The secondary objective of the study is to compare the effect of treatment with zoledronic acid to placebo on overall survival (OS), progression-free survival (PFS) and toxicity in men receiving androgen deprivation therapy for metastatic prostate cancer.

Patients are randomized to 1 of 2 treatment arms. Treatment continues in the absence of disease progression or a skeletal-related event. All patients receive concurrent androgen deprivation therapy with a GnRH agonist. Patients also receive oral calcium and (vitamin D) supplements daily. Patients progressing to androgen-independent prostate cancer proceed to the open-label therapy with zoledronic acid IV. Treatment continues for 3 weeks in the absence of disease progression or the first skeletal-related event.

Patients are followed periodically for approximately 10 years after entry on the study.

Arms: arm 1: 4mg by IV over 15 minutes every 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progression on blinded treatment before having a skeletal event may continue on open label Zoledronic acid (4 mg by IV over 15 minutes every 3 weeks). arm 2: Placebo bu IV over 15 minutes for 4 weeks in the absence of disease progression or the first skeletal-related event. Participants who progress on blinded treatment before having a skeletal event may continue on open label Zoledronic acid.
Interventions: intervention 1: zoledronic acid intervention 2: placebo intervention 3: androgen deprivation therapy intervention 4: GnRH agonist intervention 5: Calcium supplement intervention 6: Vitamin D
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive androgen deprivation therapy per SWOG-9346. All other patients will receive androgen deprivation therapy at a standard dose and schedule throughout the study. intervention 4: Patients concurrently enrolled on the Phase III study of intermittent androgen deprivation in patients with stage D2 prostate cancer will receive the GnRH agonist per SWOG-9346. All other patients will receive GnRH agonist at a standard dose and schedule throughout the study. intervention 5: Patients will receive 500 mg by mouth daily of a calcium supplement or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily. intervention 6: Patients will receive a multivitamin tablet containing 400-500 IU vitamin D by mouth daily or a combination tablet containing approximately 500 mg elemental calcium and 400-500 IU vitamin D by mouth daily.

Protocol documents: