RATIONALE: Zoledronate and estradiol may be effective in preventing bone loss. It is not yet known whether zoledronate and estradiol are more effective alone or in combination in preventing bone loss in patients who are receiving hormone therapy for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of zoledronate and estradiol alone to that of zoledronate combined with estradiol in preventing bone loss in patients who are receiving hormone therapy for prostate cancer.

Condition	Treatment or Intervention	Phase
Osteoporosis stage III prostate cancer stage IV prostate cancer	Drug: estradiol  Drug: zoledronate  Procedure: complications of therapy assessment/management  Procedure: supportive care/therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the changes in bone mineral density (BMD) and bone turnover in patients with prostate cancer undergoing gonadotropin-releasing hormone agonist therapy when treated with zoledronate vs estradiol vs zoledronate and estradiol vs placebo.
• Determine whether these regimens prevent bone loss in these patients.
• Compare the effects of these regimens on markers of bone turnover in these patients.
• Determine whether the effect of these regimens on markers of bone turnover predicts BMD response in these patients.
• Compare quality of life and vasomotor symptoms of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive zoledronate (ZA) IV and estradiol transdermally on day 1.
• Arm II: Patients receive ZA IV and placebo transdermally on day 1.
• Arm III: Patients receive placebo IV and estradiol transdermally on day 1.
• Arm IV: Patients receive placebo IV and placebo transdermally on day 1. In all arms, treatment repeats every 3 months for 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive calcium and cholecalciferol (vitamin D) supplements daily. Active or placebo transdermal estrogen patches are also worn daily.

Quality of life is assessed at baseline and then at 3, 6, and 12 months.

PROJECTED ACCRUAL: A total of 120 patients (30 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of locally advanced or metastatic prostate cancer
• No metastasis to bone
• Planned treatment with gonadotropin-releasing hormone (GNRH) agonist therapy for at least 9 months
• No osteoporosis (baseline T must be greater than 2.5)

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• No prior thrombosis
• No coronary artery disease
• No deep vein thrombosis
• No uncontrolled hypertension
• No prior cerebrovascular accident
• Electrocardiogram normal

Other

• No breast tenderness

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• See Disease Characteristics
• Prior GNRH agonist therapy allowed provided testosterone level is greater than 200 ng/dL

Radiotherapy

• Not specified

Surgery

• Not specified

New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting

Study chairs or principal investigators

Elizabeth Shane, MD,  Study Chair,  Herbert Irving Comprehensive Cancer Center   

Study ID Numbers:  CDR0000258107; CPMC-IRB-14470; NCI-G02-2129; NOVARTIS-CPMC-IRB-14470; NCT00049491
Record last reviewed:  December 2002
Last Updated:  December 6, 2004
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049491
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08