Clinical trial NCT00058188: Zolendronate for the Prevention of Bone Loss in Men w/ Prostate CA on Long-Term Androgen Deprivation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Osteoporosis
Prostate Cancer
Keywords: osteoporosis
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2003-04-09
Enrollment: 53
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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)

Primary outcomes:
measure: Bone Density Change as Measured by Dual-energy X-ray Absorptiometry From Baseline to 13 Months
timeFrame: Bone scan taken at baseline and month 13
Secondary outcomes:
measure: 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
timeFrame: Lumbar spine and hip bone density taken at baseline and month 13.
measure: Markers of Bone Formation and Resorption
timeFrame: Bone alkaline phosphatase taken at baseline, month 6 and month 13.
measure: Incidence of Skeletal Events (Pathologic and Non-pathologic Bone Fractures, Spinal Cord Compression, Surgery to Bone, and Radiotherapy to Bone)
timeFrame: 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.
measure: Incidence of New or Progressive Bone Metastatic Disease
timeFrame: Serum osteocalcin and serum bone alkaline phosphatase taken at baseline, month 6 and month 13.
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger Hospital of Cook County
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Charles L. Bennett, MD, PhD
role: STUDY_CHAIR
References: