Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Special Category: CTSU trial, NCI Web site featured trial

Objectives

Primary

1. Compare the time to first skeletal-related events in patients with prostate cancer and bone metastases undergoing androgen deprivation therapy when treated with zoledronate vs placebo.

Secondary

1. Compare the overall and progression-free survival of patients treated with these regimens.
2. Compare the toxic effects in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the prostate

• No small cell, neuroendocrine, or transitional cell carcinomas

• At least 1 bone metastasis by bone scan, MRI, CT scan, or plain radiographs
  • Indeterminate lesions should be confirmed by a second imaging method
  • At least 1 bone metastasis with no prior irradiation

• Concurrent androgen deprivation therapy required, defined as any of the following:
  • Bilateral orchiectomy
  • Gonadotropin-releasing hormone (GnRH) agonist with or without an antiandrogen

Prior/Concurrent Therapy:

Biologic therapy

• Concurrent standard biologic response modifiers allowed during open-label therapy only

Chemotherapy

• Concurrent standard cytotoxic chemotherapy allowed during open-label therapy only

Endocrine therapy

• See Disease Characteristics
• Prior neoadjuvant and/or adjuvant hormonal therapy allowed provided duration of therapy was no more than 6 months AND therapy was discontinued more than 6 months before study entry
• No more than 6 months since initiation of any of the following hormonal therapies:
  • Orchiectomy
  • GnRH agonist (e.g., leuprolide, goserelin, or triptorelin)
  • Estrogen therapy
  • Antiandrogens (e.g., bicalutamide, flutamide, or nilutamide)
  • Any other therapy known to lower testosterone levels or inhibit testosterone effect
• No intermittent androgen deprivation therapy except for patients concurrently enrolled on SWOG-9346
• Concurrent palliative corticosteroids allowed during open-label therapy only
• Concurrent standard hormonal agents allowed during open-label therapy only

Radiotherapy

• See Disease Characteristics
• No prior radiopharmaceuticals
• At least 4 weeks since prior radiotherapy
• Concurrent standard radiotherapy to extraskeletal tumor sites allowed during open-label therapy only

Surgery

• See Disease Characteristics

Other

• No prior bisphosphonates
• No prior denosumab
• No other concurrent agents expected to alter osteoclast activity (e.g., denosumab, calcitonin, mithramycin, gallium nitrate, or any other bisphosphonate)
• Concurrent daily supplemental elemental calcium (500 mg) and a multivitamin containing cholecalciferol (Vitamin D) (400 IU) OR a combination tablet containing both recommended
• Concurrent standard marketed antineoplastic therapies allowed during open-label therapy only

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine clearance ≥ 30 mL/min
• Corrected calcium ≥ 8.0 mg/dL and < 11.6 mg/dL

Other

• Fertile patients must use effective contraception

Expected Enrollment

A total of 680 patients (340 per treatment arm) will be accrued for this study within 4 years.

Outcomes

Time to first skeletal related event

Overall survival
Progression-free survival
Toxicity

Outline

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). 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.

In both arms, courses repeat every 4 weeks in the absence of disease progression or a skeletal-related event. All patients receive concurrent androgen deprivation therapy. Patients also receive oral calcium and cholecalciferol (vitamin D) supplements daily.

Patients progressing to androgen-independent prostate cancer proceed to open-label therapy comprising zoledronate IV over 15 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or a skeletal-related event.

Patients are followed periodically for approximately 10 years after randomization.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Matthew Smith, MD, Protocol chair		Ph: 617-724-5257; 877-726-5130

Southwest Oncology Group

Nirmala Bhoopalam, MD, Protocol chair		Ph: 708-202-2782 Email: nirmala.bhoopalam@med.va.gov

Eastern Cooperative Oncology Group

Christopher Sweeney, MBBS, Protocol chair		Ph: 317-274-3515; 888-600-4822 Email: chsweene@iupui.edu

NCIC-Clinical Trials Group

Fred Saad, MD, FRCS, Protocol chair		Ph: 514-890-8000 ext 27466 Email: fred.saad.chum@ssss.gouv.qc.ca

Related Information

Featured trial article

Registry Information
Official Title		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
Trial Start Date		2004-01-15
Trial Completion Date		2008-01-11 (estimated)
Registered in ClinicalTrials.gov		NCT00079001
Date Submitted to PDQ		2004-01-14
Information Last Verified		2012-04-05
NCI Grant/Contract Number		CA31946

Back to Top