Zolendronate for the Prevention of Bone Loss in Men w/ Prostate CA on Long-Term Androgen Deprivation

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Zoledronate may prevent bone loss associated with long term androgen deprivation therapy. It is not yet known whether zoledronate combined with calcium is more effective than calcium alone in preventing bone loss. PURPOSE: Randomized phase III trial to compare the effectiveness of zoledronate combined with calcium with that of calcium alone in preventing bone loss in patients with stage III or stage IV prostate cancer who have received long-term androgen deprivation therapy.

Detailed Description
-----------------
OBJECTIVES: Compare bone loss in patients receiving long-term androgen deprivation therapy for stage III or IV prostate cancer when treated with supportive care with vs without zoledronate. Compare the percentage change in lumbar spine and hip bone density in patients treated with these regimens. Compare markers of bone formation and resorption in patients treated with these regimens. Compare the incidence of skeletal events (pathologic and non-pathologic bone fractures, spinal cord compression, surgery to bone, and radiotherapy to bone) in patients treated with these regimens. Compare the incidence of new or progressive bone metastatic disease in patients treated with these regimens. Compare the survival rate of patients treated with these regimens. OUTLINE: Patients are stratified according to race (black vs other). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. Arm II: Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 72 patients (36 per treatment arm) will be accrued for this study.

Official Title
-----------------
A Phase III Randomized Study of Zolendronate Bisphosphonate Therapy for the Prevention of Bone Loss in Men With Prostate Cancer Receiving Long-Term Androgen Deprivation

Conditions
-----------------
Osteoporosis, Prostate Cancer

Intervention / Treatment
-----------------
* Dietary Supplement: cholecalciferol
* Drug: calcium gluconate
* Drug: zoledronic acid


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed prostate cancer Stage III or IV disease Received at least 3 months of prior androgen deprivation therapy (no maximum amount/time) by either surgical or medical castration Medical castration may be by intermittent or continuous androgen suppression via single- or combined-drug androgen blockade Continued concurrent androgen deprivation therapy required throughout study participation No bone metastases by baseline bone scan PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 1 year Hematopoietic Not specified Hepatic Bilirubin less than 3 times upper limit of normal (ULN) AST and ALT less than 3 times ULN No chronic liver disease Renal Creatinine no greater than 2.0 mg/dL Other Fertile patients must use effective contraception No Paget's disease No Cushing's disease No hyperthyroidism No hyperprolactinemia PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Prior chemotherapy for prostate cancer allowed Endocrine therapy See Disease Characteristics More than 12 months since prior suppressive doses of thyroxine or calcitonin More than 6 months since prior corticosteroids Concurrent corticosteroids allowed (after enrollment on study) Radiotherapy Prior radiotherapy for prostate cancer allowed Surgery See Disease Characteristics Other More than 12 months since prior bisphosphonate therapy (oral or IV)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive zoledronate IV over 15 minutes on day 1 and oral calcium gluconate and oral cholecalciferol daily. Courses repeat every 3 months for 12 months in the absence of toxicity. | Dietary Supplement: cholecalciferol<br>* Given orally<br>Drug: calcium gluconate<br>* Given orally<br>Drug: zoledronic acid<br>* Given IV<br>|
| Active Comparator: Arm II<br>Patients receive oral calcium gluconate and oral cholecalciferol as in arm I. | Dietary Supplement: cholecalciferol<br>* Given orally<br>Drug: calcium gluconate<br>* Given orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Density Change as Measured by Dual-energy X-ray Absorptiometry From Baseline to 13 Months | To assess bone density change as measured by dual-energy x-ray absorptiometry | Bone scan taken at baseline and month 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Lumbar Spine and Hip Bone Density as Measured by Plain Film X-rays of Lumbar Spine and Pelvis From Baseline to 13 Months | To assess the percentage change in lumbar spine and hip bone density as measured by plain film x-rays of lumbar spine and pelvis | Lumbar spine and hip bone density taken at baseline and month 13. | 
| Markers of Bone Formation and Resorption | To assess markers of bone formation and resorption. | Bone alkaline phosphatase taken at baseline, month 6 and month 13. | 
| Incidence of Skeletal Events (Pathologic and Non-pathologic Bone Fractures, Spinal Cord Compression, Surgery to Bone, and Radiotherapy to Bone) | To assess the incidence of skeletal events (pathologic and non-pathologic bone fractures, spinal cord compression, surgery to bone, and radiotherapy to bone) | PSA taken at baseline, month 3, month 6, month 9, month 12 and month 13. CT scan of abdomen and pelvis taken at baseline and month 13. Serum testosterone, estradiol, parathyroid taken at baseline, month 6 and month 13. | 
| Incidence of New or Progressive Bone Metastatic Disease | To assess the incidence of new or progressive bone metastatic disease | Serum osteocalcin and serum bone alkaline phosphatase taken at baseline, month 6 and month 13. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteoporosis, stage III prostate cancer, stage IV prostate cancer