Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries

Study Overview
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Brief Summary
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This randomized phase II trial is studying zoledronate to see how well it works compared to observation in maintaining bone mineral density in patients who are undergoing surgery to remove both ovaries. Zoledronate may prevent bone loss in patients who are undergoing surgery to remove the ovaries.

Detailed Description
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PRIMARY OBJECTIVE: I. Compare the effect of zoledronate vs observation on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries) in patients undergoing excision of both ovaries. SECONDARY OBJECTIVE: I. Compare the change in bone mineral density of the bilateral hip in patients treated with these regimens. TERTIARY OBJECTIVE: I. Compare the effect of zoledronate vs observation on biochemical markers of bone resorption and bone formation (N-telopeptide and bone specific alkaline phosphatase) during 1 year of treatment. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. All patients undergo surgery, with removal of both ovaries, in month 1. All patients are requested to take calcium supplements twice daily and a multivitamin containing vitamin D once daily beginning in month 1 and continuing for up to 18 months. ARM I: Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. ARM II: Patients are observed for 18 months after surgery. In both arms, patients complete physical activity questionnaires at baseline and in months 3, 9, 15, and 18. Patients undergo bone mineral density test of lumbar spine and total hip at baseline and in months 9 and 18. Patients also undergo blood collection at baseline and periodically during the study for biomarker studies.

Official Title
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A Phase II Randomized Study of the Effect of Zoledronic Acid Versus Observation on Bone Mineral Density of the Lumbar Spine in Women Who Elect to Undergo Surgery That Results in Removal of Both Ovaries

Conditions
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Hereditary Breast and Ovarian Cancer Syndrome, Osteoporosis, Ovarian Carcinoma

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Drug: Zoledronic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have elected to undergo, or who have undergone (within 8 weeks) a surgical procedure that results (at minimum) in the absence of both ovaries Patients enrolled in the screening arm of GOG-0199 who decide to undergo surgery are potentially eligible for GOG-0215 Baseline bone mass density (BMD) T-Score ? -1.5 (no more than 1.5 standard deviation below the mean value for young adults) on both the total lumbar spine (L1-L4 region, not individual bones) and bilateral hip Patients who had/have at least 1 intact ovary at the time of surgery are eligible No prior distant metastatic malignant disease within the past 5 years Patients treated for stage M1 (any T, any N) diagnosis in the past 5 years are ineligible Patients who achieved a complete response after treatment for rM0 (any T, any N) within the past 5 years are eligible Premenopausal* Last menstrual cycle occurred < 12 months prior to study enrollment GOG performance status 0-2 Creatinine clearance > 60 mL/min No clinical or radiological evidence of existing fracture of the lumbar spine or bilateral hip No history of hip of spine fracture with low-intensity trauma or not associated with trauma No uncontrolled seizure disorder associated with falls No diseases that influence bone metabolism, including any of the following: Paget?s disease Osteogenesis imperfecta Uncontrolled thyroid or parathyroid dysfunction within 12 months prior to study entry No other nonmalignant systemic disease, including any of the following: Uncontrolled infection Uncontrolled type 2 diabetes mellitus Cardiovascular, renal, hepatic, or lung disease that would prevent prolonged follow-up History of thrombosis or thromboembolism allowed No known HIV positivity No known hypersensitivity to zoledronate or other bisphosphonates No psychiatric, psychological, or other conditions that prevent fully informed consent No other active malignancy except nonmelanoma skin cancer No history of any medical condition that places the patient at risk for donating blood for research purposes (e.g., chronic infectious diseases, sever anemia, or hemophilia) Not pregnant Negative pregnancy test No current active dental problems, including any of the following: Infection of the teeth or jawbone (maxilla or mandible) Dental or fixture trauma Current or prior diagnosis of osteonecrosis of the jaw Exposed bone in the mouth Slow healing after dental procedures No recent (within 6 weeks) or planned dental or jaw surgery (e.g., extraction or implants) No prior treatment for osteoporosis No adjuvant radiotherapy within the past 31 days No chemotherapy within the past 30 days No prior surgery to the hip or spine No prior systemic sodium fluoride for > 3 months during the past 2 years No more than 30 days use in the past 12 months and no concurrent tamoxifen, raloxifene, or any other selective estrogen-receptor modulator (SERM) More than 12 months since prior and no concurrent endocrine therapy Insulin and/or oral antidiabetic medications allowed Thyroid hormone replacement allowed More than 12 months since prior and no concurrent estrogen or hormone replacement therapy (estrogen plus progesterone or estrogen alone) Prior or concurrent oral contraceptives allowed Systemic (oral) hormone replacement therapy following surgery not allowed Vaginal (non-systemic) estrogen allowed More than 12 months since prior and no concurrent oral or IV bisphosphonate More than 12 months since prior and no concurrent anabolic steroids or growth hormone More than 12 months since prior and no concurrent systemic corticosteroids Concurrent short term corticosteroid therapy (to prevent/treat chemotherapy-induced nausea/vomiting) allowed More than 6 months since prior and no concurrent Tibolone More than 2 weeks since prior and no concurrent drugs known to affect the skeleton (e.g., calcitonin, mithramycin, or gallium nitrate) No concurrent chemotherapy or radiotherapy No concurrent aromatase inhibitors Concurrent enrollment on protocol GOG-0199 allowed
Sexes Eligible for Study
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Female

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (zoledroic acid)<br>Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Zoledronic Acid<br>* Given IV<br>* Other names: Zometa;|
| No Intervention: Arm II (clinical observation)<br>Patients are observed for 18 months after surgery. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 9 Months | To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 9 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA). | 9 Months | 
| Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 18 Months | To compare the effect of zoledronic acid administered every 6 months on bone loss associated with surgery (at a minimum, any surgical procedure that results in removal of both ovaries), as compared with observation alone. This is to be evaluated by measuring the change from baseline to 18 months in bone mineral density (BMD) of the lumbar spine, specifically L1-L4 dual energy X-ray absorptiometry (DEXA). | 18 months | 
| Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Right Hip | To compare the effect of zoledronic acid on the change in BMD of the right hip following treatment, evaluated by measuring the change from baseline to 18 months | 18 months | 
| Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip | To compare the effect of zoledronic acid on the change in BMD of the left hip following treatment, evaluated by measuring the change from baseline to 18 months | 18 months |