Osteoporosis, Prostate Cancer
Conditions
Keywords
osteoporosis, stage III prostate cancer, stage IV prostate cancer
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.
Interventions
DIETARY_SUPPLEMENTcholecalciferol
Given orally
Given orally
DRUGzoledronic acid
Given IV
Sponsors
Novartis
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Density Change as Measured by Dual-energy X-ray Absorptiometry From Baseline to 13 Months | Bone scan taken at baseline and month 13 | To assess bone density change as measured by dual-energy x-ray absorptiometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Lumbar spine and hip bone density taken at baseline and month 13. | To assess the percentage change in lumbar spine and hip bone density as measured by plain film x-rays of lumbar spine and pelvis |
| Markers of Bone Formation and Resorption | Bone alkaline phosphatase taken at baseline, month 6 and month 13. | To assess markers of bone formation and resorption. |
| 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. | To assess the incidence of skeletal events (pathologic and non-pathologic bone fractures, spinal cord compression, surgery to bone, and radiotherapy to bone) |
| Incidence of New or Progressive Bone Metastatic Disease | Serum osteocalcin and serum bone alkaline phosphatase taken at baseline, month 6 and month 13. | To assess the incidence of new or progressive bone metastatic disease |
Countries
United States
Participant flow
Recruitment details
PIs departure from the institution was sudden and due unforeseen serious circumstances. Due to this, no data was collected for this study nor can be reported on.
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Zoledronate, Calcium and Cholecalciferol 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.
cholecalciferol: Given orally
calcium gluconate: Given orally
zoledronic acid: Given IV | 0 |
| Treatment With Calcium and Cholecalciferol Patients receive oral calcium gluconate and oral cholecalciferol as in arm I.
cholecalciferol: Given orally
calcium gluconate: Given orally | 0 |
| Total | 0 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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
Time frame: Bone scan taken at baseline and month 13
Population: Due to the unique situation of the PI, no data was collected for this study nor can be reported on.
Secondary
Incidence of New or Progressive Bone Metastatic Disease
To assess the incidence of new or progressive bone metastatic disease
Time frame: Serum osteocalcin and serum bone alkaline phosphatase taken at baseline, month 6 and month 13.
Population: Due to the unique situation of the PI, no data was collected for this study nor can be reported on.
Secondary
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)
Time frame: 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.
Population: Due to the unique situation of the PI, no data was collected for this study nor can be reported on.
Secondary
Markers of Bone Formation and Resorption
To assess markers of bone formation and resorption.
Time frame: Bone alkaline phosphatase taken at baseline, month 6 and month 13.
Population: Due to the unique situation of the PI, no data was collected for this study nor can be reported on.
Secondary
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
Time frame: Lumbar spine and hip bone density taken at baseline and month 13.
Population: Due to the unique situation of the PI, no data was collected for this study nor can be reported on.