|Phase II||Biomarker/Laboratory analysis, Natural history/Epidemiology, Prevention||Closed||Not specified||NCI, Other||CDR0000462217|
GOG-0215, NOVARTIS-GOG-0215, NCI-06-C-0204, NCI-P6966, 0215, NCT00305695
RATIONALE: Zoledronate may prevent bone loss in patients who are undergoing surgery to remove the ovaries.
PURPOSE: 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.
Further Study Information
- 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.
- 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
- 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 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
PRIOR CONCURRENT THERAPY:
- 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
Trial Lead Organizations/Sponsors
Gynecologic Oncology GroupNational Cancer Institute
|David Samuel Alberts||Study Chair|
|Lisa M. Hess|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00305695
Information obtained from ClinicalTrials.gov on November 20, 2012
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