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

Phase 2

Completed

Conditions: Osteoporosis
Ovarian Carcinoma
Hereditary Breast and Ovarian Cancer Syndrome

Interventions: Other: Laboratory Biomarker Analysis
Drug: Zoledronic Acid

Registration Number: NCT00305695

Lead Sponsor: Gynecologic Oncology Group

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 160

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (zoledroic acid)	Laboratory Biomarker Analysis	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.
Arm I (zoledroic acid)	Zoledronic Acid	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.

Primary Outcome Measures

Name	Time	Method
Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 9 Months	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).
Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 18 Months	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).
Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Right Hip	18 months	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
Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip	18 months	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

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (95): Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Banner University Medical Center - Tucson
🇺🇸
Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
🇺🇸
Tucson, Arizona, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸
Burbank, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸
Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸
Los Angeles, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸
Orange, California, United States
Stanford Cancer Institute Palo Alto
🇺🇸
Palo Alto, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
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Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States