Zoledronate Plus Standard Therapy Compared With Placebo Plus Standard Therapy to Prevent Bone Metastases in Patients With Recurrent Prostate Cancer That Has No Symptoms

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005073
Recruitment Status : Terminated
First Posted : June 18, 2004
Last Update Posted : May 1, 2013
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

RATIONALE: Zoledronate may be able to prevent bone metastases caused by prostate cancer. It is not yet known if zoledronate is effective in preventing the spread of prostate cancer to the bones.

PURPOSE: Randomized phase III trial to determine the effectiveness of zoledronate plus standard therapy in preventing bone metastases in patients who have recurrent prostate cancer that is not causing symptoms.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: zoledronic acid Phase 3

Detailed Description:

OBJECTIVES: I. Compare the bone metastases free and overall survival in patients with asymptomatic recurrent prostate cancer treated with zoledronate vs placebo at different time points. II. Compare the time to first skeletal related events (pathological fractures, surgery to prevent or treat pathological fractures, spinal cord compression, and radiotherapy to bone) and skeletal morbidity rate in patients treated with these 2 regimens. III. Assess quality of life and pain in these patients treated with these 2 regimens.

OUTLINE: This is a randomized, double blind, placebo controlled, open label, multicenter study. Patients are stratified by prior local treatment (noncurative vs curative) and time interval between surgical castration or initiation of LHRH agonists and trial entry (less than 1 year vs 1-2 years vs greater than 2 years). Patients are randomized to 1 of 2 treatment arms: Arm I: Patients receive zoledronate IV over 15 minutes on day 1. Arm II: Patients receive placebo IV over 15 minutes on day 1. Both arms: Treatment repeats every 4 weeks in the absence of documented bone metastasis, disease progression, or unacceptable toxicity. All patients with documented bone metastases receive zoledronate as in arm I through year 4. All patients receive oral calcium and oral vitamin D daily. Patients who received LHRH agonists instead of surgical castration prior to study continue LHRH agonist therapy during study. Quality of life and pain are assessed before each treatment. Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 500 patients (250 per arm) will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 544 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Randomized Double-Blind Placebo Controlled Phase III Trial Evaluating Zoledronate Plus Standard Therapy Versus Placebo Plus Standard Therapy in Patients With Recurrent Carcinoma of the Prostate Who Are Asymptomatic With Castrate Levels of Testosterone and Have Rising PSA Levels Without Radiologically-Evident Metastatic Disease
Study Start Date : September 1999
Actual Primary Completion Date : March 2003
Actual Study Completion Date : March 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

DISEASE CHARACTERISTICS: Histologically proven asymptomatic recurrent prostate cancer Prior local treatment status Curatively treated OR Locally advanced disease noncuratively treated with LHRH agonist therapy Currently receiving 1 line of hormonal therapy (with LHRH agonists or surgical castration) and failing treatment with rising PSA only Patients who received LHRH agonists instead of surgical castration continue to receive LHRH agonist during study Biochemical progression documented by 3 consecutively rising PSA measurements, each at least 2 weeks apart, with the last measurement being 50% or greater than the nadir PSA achieved after the last therapeutic maneuver (first line hormonal therapy as noted above) PSA (50% increased values) greater than 4 ng/mL for patients with intact prostates and greater than 0.8 ng/mL for post-prostatectomy patients Rising PSA for less than 10 months Castrate levels of testosterone (less than 30 ng/dL) No bone or visceral metastases by bone scan and CT scan of abdomen and pelvis (except localized abnormalities and pelvic lymph node and soft tissue disease) No CNS or leptomeningeal involvement

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 90-100% Life expectancy: Greater than 6 months Hematopoietic: WBC at least 3,000/mm3 Absolute neutrophil count at least 1,500/mm3 Hemoglobin at least 8.0 g/dL Platelet count at least 75,000/mm3 Hepatic: Liver function tests no greater than 2.5 times upper limit of normal (ULN) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease with uncontrolled and/or unstable cardiac or coronary artery disease Other: No other malignancy within the past 5 years that would confound the etiology of metastatic disease except curatively treated nonmelanomatous skin cancer No other nonmalignant disease that would confound evaluation or preclude compliance Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior systemic biologic anticancer therapy Chemotherapy: No prior chemotherapy Concurrent chemotherapy such as estramustine containing regimens or mitoxantrone allowed at the discretion of the protocol investigator Endocrine therapy: See Disease Characteristics No prior systemic hormonal anticancer therapy except LHRH antagonists and/or nonsteroidal antiandrogens (e.g., flutamide, bicalutamide, or nilutamide) Concurrent aminoglutethimide, prednisone, or diethylstilbestrol or other estrogens allowed at the discretion of the protocol investigator Radiotherapy: At least 6 weeks since prior palliative radiotherapy Surgery: See Disease Characteristics Other: No other prior systemic anticancer therapy At least 4 weeks since other prior investigational drugs No other concurrent bisphosphonate agent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005073

United States, California
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Chair: Fairooz F. Kabbinavar, MD Jonsson Comprehensive Cancer Center

Publications of Results:
Responsible Party: Novartis Pharmaceuticals Identifier: NCT00005073     History of Changes
Other Study ID Numbers: NOVARTIS-CZOL4460704
CDR0000067678 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: June 18, 2004    Key Record Dates
Last Update Posted: May 1, 2013
Last Verified: April 2013

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Zoledronic acid
Bone Density Conservation Agents
Physiological Effects of Drugs