Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

OBJECTIVES:

Primary

• 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

• Compare the overall and progression-free survival of patients treated with these regimens.

• Compare the toxic effects in patients treated with these regimens.

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.

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

Eligibility 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

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

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Matthew R. Smith

Study Chair

Nirmala Bhoopalam

Study Chair

Christopher Sweeney

Study Chair

Fred Saad

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00079001
Information obtained from ClinicalTrials.gov on February 20, 2013

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