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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

Phase 2
Open (Enrolling)
Hereditary Breast/Ovarian Cancer (brca1, brca2), Osteoporosis, Ovarian Cancer

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Trial Information

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



- 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.


- Compare the change in bone mineral density of the bilateral hip in patients treated
with these regimens.


- 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.

PROJECTED ACCRUAL: A total of 222 patients will be accrued for this study.

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

- 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 NOTE: *In
unclear cases premenopausal status may be determined by follicle stimulating
hormone level AND must be ≤ 20 U/L

- 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

- 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

- 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

- 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

- 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

- 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

- 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

Type of Study:


Study Design:


Outcome Measure:

Bone mineral density of the lumbar spine as measured by dual-energy x-ray absorptiometry (DEXA) scan at baseline (may be before surgery) and 9 and 18 months after surgery

Safety Issue:


Principal Investigator

David S. Alberts, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Arizona


United States: Federal Government

Study ID:




Start Date:

November 2005

Completion Date:

Related Keywords:

  • Hereditary Breast/Ovarian Cancer (brca1, brca2)
  • Osteoporosis
  • Ovarian Cancer
  • osteoporosis
  • hereditary breast/ovarian cancer (BRCA1, BRCA2)
  • ovarian epithelial cancer
  • Osteoporosis
  • Ovarian Neoplasms



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