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

Phase 3

Completed

Conditions: Metastatic Cancer
Prostate Cancer

Interventions: Drug: zoledronic acid
Other: placebo
Drug: androgen deprivation therapy
Drug: GnRH agonist
Dietary Supplement: Calcium supplement
Dietary Supplement: Vitamin D

Registration Number: NCT00079001

Lead Sponsor: Alliance for Clinical Trials in Oncology

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 645

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zoledronic acid + androgen deprivation therapy	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).
Zoledronic acid + androgen deprivation therapy	Vitamin D	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).
Zoledronic acid + androgen deprivation therapy	zoledronic acid	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).
Zoledronic acid + androgen deprivation therapy	androgen deprivation therapy	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 + androgen deprivation therapy	placebo	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.
Placebo + androgen deprivation therapy	androgen deprivation therapy	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.
Placebo + androgen deprivation therapy	Calcium supplement	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.
Placebo + androgen deprivation therapy	Vitamin D	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 + androgen deprivation therapy	GnRH agonist	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 + androgen deprivation therapy	GnRH agonist	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.

Primary Outcome Measures

Name	Time	Method
Time to First Skeletal Related Event	Up to 10 years	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 10 years	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	Up to 10 years	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.

Trial Locations

Locations (240): Providence Cancer Center at Providence Hospital
🇺🇸
Mobile, Alabama, United States
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸
Fort Smith, Arkansas, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Veterans Affairs Medical Center - Loma Linda (Pettis)
🇺🇸
Loma Linda, California, United States
Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
🇺🇸
Pomona, California, United States
Saint Helena Hospital
🇺🇸
Saint Helena, California, United States
Salinas Valley Memorial Hospital
🇺🇸
Salinas, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸
San Francisco, California, United States
Ruby L. Golleher Cancer Program at Presbyterian Intercommunity Hospital
🇺🇸
Whittier, California, United States
Yale Cancer Center
🇺🇸
New Haven, Connecticut, United States
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Providence Cancer Center at Providence Hospital
🇺🇸Mobile, Alabama, United States