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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2010 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00305695
First received: March 21, 2006
Last updated: May 5, 2010
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Hereditary Breast/Ovarian Cancer (brca1, brca2)
Osteoporosis
Ovarian Cancer
Drug: zoledronic acid
Other: clinical observation
Phase 2

Study Type: Observational
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bone mineral density of the total hip as measured by DEXA scan at baseline (may be before surgery) and 9 and 18 months after surgery [ Designated as safety issue: No ]

Estimated Enrollment: 222
Study Start Date: November 2005
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Arm I
Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.
Drug: zoledronic acid
Given IV
Arm II
Patients are observed for 18 months after surgery.
Other: clinical observation
Patients are observed for 18 months after surgery.

Detailed Description:

OBJECTIVES:

Primary

  • 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

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

Tertiary

  • 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305695

  Show 67 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Study Chair: David S. Alberts, MD University of Arizona
Investigator: Larissa Korde, MD, MPH National Cancer Institute (NCI)
Investigator: Gus Rodriguez, MD NorthShore University HealthSystem Research Institute
Investigator: Lisa M. Hess, PhD University of Arizona
  More Information

Additional Information:
No publications provided

Responsible Party: Philip J. DiSaia, Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00305695     History of Changes
Other Study ID Numbers: CDR0000462217, GOG-0215, NOVARTIS-GOG-0215, NCI-06-C-0204, NCI-P6966
Study First Received: March 21, 2006
Last Updated: May 5, 2010
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
osteoporosis
hereditary breast/ovarian cancer (BRCA1, BRCA2)
ovarian epithelial cancer

Additional relevant MeSH terms:
Ovarian Neoplasms
Osteoporosis
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014