Zometa on Bone Mineral Density in Prostate Cancer Patients Undergoing Androgen Ablation Therapy

Study Overview
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Brief Summary
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The purpose of this research is to determine the effect of timing of Zometa® administration on bone mineral density of the lumbar spine and femoral neck in men undergoing androgen deprivation therapy for prostate adenocarcinoma. In addition, the researchers will also determine the effects of treatment with Zometa® on peripheral blood markers of bone turnover, on peripheral blood gd T-cell frequencies and function, and to determine if the above treatments elicit prostate antigen-specific IgG immune responses. The effects of the above treatments on serial serum PSA measurements will also be examined.

Detailed Description
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Castration by GnRH agonist therapy with or without androgen antagonists has been a mainstay for advanced prostate cancer. One of the most significant side effects of the use of androgen ablative therapies has been a decrease in bone mineral density, potentially placing patients at greater risk of osteoporosis and bone fractures. It is prudent to anticipate this adverse effect of therapy and to minimize its severity with appropriate and timely pharmacologic intervention. Zometa is a bisphosphonates and bisphosphonates are effective inhibitors of osteoclastic bone resorption. Recent studies have shown that other bisphosphonates were able to reduce the bone loss observed after 24 and 48 weeks of treatment with a GnRH analogue. An unanswered question remains, however, in how frequently these agents should be employed in clinical practice. This is a three-arm randomized trial of Zometa® on bone mineral density in subjects with stage D prostate cancer undergoing androgen ablation therapy. If subjects are enrolled in Arm 1, the GnRH analogue would be administered every 3 months for 1 year. Four milligrams of Zometa® would be administered IV over 15 minutes 7 days prior to beginning androgen deprivation therapy. If subjects are enrolled in Arm 2, the GnRH analogue would be administered every 3 months for one year, and 4 mg of Zometa® would be administered IV over 15 minutes at month 6. If subjects are enrolled in Arm 3, the GnRH analogue is administered every 3 months for 1 year, with 4 mg of Zometa® administered IV over 15 minutes monthly for 6 months, beginning at month 6.

Official Title
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Phase II Trial of Zometa on Bone Mineral Density on Patients With Stage D Prostate Cancer Undergoing Androgen Ablation Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Zometa
* Drug: zometa
* Drug: Zometa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have a histologic diagnosis of adenocarcinoma of the prostate. For patients without clinical metastasis treated by surgery, serum PSA values must be > 0.2 ng/ml by two measurements at least two weeks apart. In patients treated with ablative radiation therapy without clinical metastasis, three consecutive increases in serum PSA must be documented, with at least a one-month interval between values with the final PSA > 2ng/m as evidence of biochemical PSA failure. P Patients who have not had prior primary therapy such as radiation or surgery, are required to have a detectable PSA of at least 0.2 ng/ml. Patients with evidence of metastatic disease are eligible irrespective of serum PSA level. Prior history of a second malignancy is allowed if treated with curative intent and patient has been free of disease greater than five years ECOG performance status of < 2. Exclusion Criteria: Prior treatment with a GnRH analogue or anti-androgen. Evidence of immunosuppression or have been treated with immunosuppressive therapy, such as chemotherapy, chronic treatment dose corticosteroids, or radiation therapy to bones, within 6 months of study enrollment Current or treatment within 4 weeks with estrogen or estrogenic agents (including herbal compound PC-SPES) Current or treatment within 4 weeks with herbal compounds for prostate cancer such as PC-SPES or saw palmetto Current or treatment within 4 weeks with megestrol Current or prior treatment with a bisphosphonate, calcitonin, or other bone resorptive/anabolic agents Current use of oral corticosteroids or any such use within the past 6 months Current use of potentially bone-toxic anticonvulsants (phenytoin, or carbamazepine) History of orchiectomy Hypocalcemia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy | Drug: Zometa<br>* GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given 7 days prior to beginning androgen deprivation therapy<br>* Other names: zolodex;|
| Active Comparator: 2<br>GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6 | Drug: zometa<br>* GnRH analogue 3-mo depot - q3 months for 1 yr andZometa 4 mg IV over 15 min x 1, given at mo 6<br>* Other names: zolodex;|
| Active Comparator: 3<br>GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6. | Drug: Zometa<br>* GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min, given monthly x 6 months, beginning in month 6.<br>* Other names: zolodex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Who Had Either an Increase or Decrease on Bone Mineral Density of the Lumbar Spine and Femoral Neck in Men Undergoing Androgen Deprivation Therapy for Prostate Adenocarcinoma. | Effects on bone mineral density were measured at four locations at six month intervals for 24 months. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover. | Serum bone-specific alkaline phosphatase was collected as the blood marker of bone turnover. | 2 years | 
| Number of Subjects Had a Significant Change in Immune Markers. | Immune markers were measured by isolating gamma-delta T cells one month after treatment with zoledronic acid. | 2 Years | 
| Number of Subjects With Decreases in Prostate Specific Antigen (PSA) After Zoledronic Acid Prior to Beginning Androgen Deprivation Therapy | PSA response was measured by observing the serum PSA one week after beginning zoledronic acid and prior to beginning androgen deprivation therapy. Arm 2 and Arm 3 were not able to be assessed for this endpoint as all subjects were on androgen deprivation prior to receiving zoledronic acid. | 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone mineral density