Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Prostatic Neoplasms

Adenocarcinoma

Recurrence

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Bone Density Conservation Agents

Micronutrients

Vitamins

Mineral

Androgens

Vitamin D

Cholecalciferol

Calcium

Calcium, Dietary

Zoledronic Acid

Trace Elements

Hormones

Hormone Antagonists

Vitamin D3

Calciferol

Calcium Supplement

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).

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.

zoledronic acid

placebo

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.

androgen deprivation therapy

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.

GnRH agonist

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.

Calcium supplement

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.

Matthew R. Smith, MD, PhD

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.

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.

Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases

A Randomized Double-Blind, Placebo-Controlled Phase III Study of Early Versus Standard Zoledronic Acid to Prevent Skeletal Related Events in Men With Prostate Cancer Metastatic to Bone

Time to first skeletal related event (SRE) was defined as the time from randomization to first skeletal event. Skeletal events are defined as radiation to bone, clinical fracture, surgery to bone and spinal cord compression and death due to prostate cancer. The median with 95% CI was estimated using the Kaplan Meier method.

Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.

Progression Free Survival (PFS) was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method.

Progression is defined as one or more of the following: new bone metastases, biochemical progression of PSA, treatment with radiation therapy while on treatment.

National Cancer Institute (NCI)

SWOG Cancer Research Network

Eastern Cooperative Oncology Group

NCIC Clinical Trials Group

Novartis Pharmaceuticals

Alliance for Clinical Trials in Oncology

All patients that reported adverse events were used to summarize the adverse events, data is available on 618 participants. Participants that were not assessed for adverse events were not included in the adverse event table.

Zoledronic Acid + Androgen Deprivation Therapy

Placebo + Androgen Deprivation Therapy

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Canada

Region of Enrollment

Classifies patients according to their functional impairment. Scores range from 0 (fully active) to 5 (death).

ECOG Performance Status

Prior Skeletal Related Event

Matthew Smith, MD, PhD

The null hypothesis was that the hazard ratio is greater than or equal to 1.0 versus the alternative hypothesis that the hazard ratio is less than 0.77. With a target of 470 SREs, log-rank statistic had 88% power to detect a 23% decrease in hazard of SRE (equivalent to an increase in median time to SRE from 30 months to 39 months), assuming a one-sided type I error rate of .05.

Time to First Skeletal Related Event

Overall Survival

Progression-free Survival

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases	NCT00079001	Metastatic Canc... Prostate Cancer	zoledronic acid placebo androgen depriv... GnRH agonist Calcium supplem... Vitamin D	18 Years -	Alliance for Clinical Trials in Oncology
Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases	NCT00079001	Metastatic Canc... Prostate Cancer	zoledronic acid placebo androgen depriv... GnRH agonist Calcium supplem... Vitamin D	18 Years -	Alliance for Clinical Trials in Oncology
Zoledronate in Preventing Skeletal (Bone)-Related Events in Men Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases	NCT00079001	Metastatic Canc... Prostate Cancer	zoledronic acid placebo androgen depriv... GnRH agonist Calcium supplem... Vitamin D	18 Years -	Alliance for Clinical Trials in Oncology

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