Prostate Cancer
Conditions
Keywords
bone mineral density
Brief summary
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
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.
Interventions
Sponsors
Novartis Pharmaceuticals
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 2 years | Effects on bone mineral density were measured at four locations at six month intervals for 24 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover. | 2 years | Serum bone-specific alkaline phosphatase was collected as the blood marker of bone turnover. |
| Number of Subjects Had a Significant Change in Immune Markers. | 2 Years | Immune markers were measured by isolating gamma-delta T cells one month after treatment with zoledronic acid. |
| Number of Subjects With Decreases in Prostate Specific Antigen (PSA) After Zoledronic Acid Prior to Beginning Androgen Deprivation Therapy | 2 Years | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were screened and enrolled at the University of Wisconsin Carbone Cancer Center from April 2003 until March 2011.
Pre-assignment details
Of the 44 subjects enrolled, one withdrew from the study prior to receiving any study treatment. As a result there were 43 subjects who received at least one dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Zometa Given 7 Days Prior to Beginning ADT 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 | 14 |
| Zometa Given at Month 6 GnRH analogue 3-mo depot - q3 months for 1 yr and Zometa 4 mg IV over 15 min x 1, given at mo 6 | 15 |
| Zometa Given Monthly x 6 Months 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. | 14 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Zometa Given Monthly x 6 Months | Total | Zometa Given 7 Days Prior to Beginning ADT | Zometa Given at Month 6 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 11 Participants | 3 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 32 Participants | 11 Participants | 11 Participants |
| Gleason Score of 8 or more | 8 participants | 15 participants | 3 participants | 4 participants |
| Participants with evidence of osteopenia/osteoporosis | 5 participants | 15 participants | 6 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 14 Participants | 43 Participants | 14 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 14 | 15 / 15 | 15 / 15 |
| serious Total, serious adverse events | 2 / 14 | 2 / 15 | 2 / 15 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zometa Given 7 Days Prior to Beginning ADT | 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. | 14 participants |
| Zometa Given at Month 6 | 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. | 15 participants |
| Zometa Given Monthly, Months 6-11 | 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. | 15 participants |
Secondary
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.
Time frame: 2 Years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zometa Given 7 Days Prior to Beginning ADT | Number of Subjects Had a Significant Change in Immune Markers. | 0 participants |
| Zometa Given at Month 6 | Number of Subjects Had a Significant Change in Immune Markers. | 0 participants |
| Zometa Given Monthly, Months 6-11 | Number of Subjects Had a Significant Change in Immune Markers. | 0 participants |
Secondary
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.
Time frame: 2 Years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zometa Given 7 Days Prior to Beginning ADT | Number of Subjects With Decreases in Prostate Specific Antigen (PSA) After Zoledronic Acid Prior to Beginning Androgen Deprivation Therapy | 0 participants |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zometa Given 7 Days Prior to Beginning ADT | The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover. | 0 participants |
| Zometa Given at Month 6 | The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover. | 0 participants |
| Zometa Given Monthly, Months 6-11 | The Number of Subjects Who Had a Significant Increase of Peripheral Blood Markers of Bone Turnover. | 0 participants |