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

March 9, 2020 updated by: Gynecologic Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic in Arizona
      • Tucson, Arizona, United States, 85719
        • Banner University Medical Center - Tucson
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center-North Campus
    • California
      • Burbank, California, United States, 91505
        • Providence Saint Joseph Medical Center/Disney Family Cancer Center
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente Los Angeles Medical Center
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center
      • Orange, California, United States, 92868
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Institute Palo Alto
      • Sacramento, California, United States, 95817
        • University of California Davis Comprehensive Cancer Center
      • San Diego, California, United States, 92103
        • University of California San Diego
    • Colorado
      • Aurora, Colorado, United States, 80010
        • Colorado Gynecologic Oncology Group
      • Boulder, Colorado, United States, 80301
        • Boulder Community Hospital
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Denver, Colorado, United States, 80218
        • SCL Health Saint Joseph Hospital
      • Denver, Colorado, United States, 80220
        • Rose Medical Center
      • Greeley, Colorado, United States, 80631
        • North Colorado Medical Center
      • Loveland, Colorado, United States, 80539
        • McKee Medical Center
      • Thornton, Colorado, United States, 80229
        • North Suburban Medical Center
      • Wheat Ridge, Colorado, United States, 80033
        • SCL Health Lutheran Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Hospital
      • New Britain, Connecticut, United States, 06050
        • The Hospital of Central Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Beebe Medical Center
      • Newark, Delaware, United States, 19718
        • Christiana Care Health System-Christiana Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • MedStar Washington Hospital Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Holy Cross Hospital
      • Jupiter, Florida, United States, 33458
        • Jupiter Medical Center
      • Orlando, Florida, United States, 32806
        • UF Cancer Center at Orlando Health
    • Hawaii
      • Honolulu, Hawaii, United States, 96859
        • Tripler Army Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
      • Winfield, Illinois, United States, 60190
        • Northwestern Medicine Central DuPage Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Indianapolis, Indiana, United States, 46260
        • Saint Vincent Hospital and Health Care Center
      • South Bend, Indiana, United States, 46601
        • Memorial Hospital of South Bend
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kansas
      • Overland Park, Kansas, United States, 66209
        • Menorah Medical Center
      • Overland Park, Kansas, United States, 66213
        • Saint Luke's South Hospital
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Baptist Health Lexington
      • Louisville, Kentucky, United States, 40202
        • Norton Hospital Pavilion and Medical Campus
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • MedStar Franklin Square Medical Center/Weinberg Cancer Institute
      • Elkton, Maryland, United States, 21921
        • Union Hospital of Cecil County
    • Michigan
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital-Royal Oak
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64116
        • North Kansas City Hospital
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
      • Kansas City, Missouri, United States, 64132
        • Research Medical Center
      • Kansas City, Missouri, United States, 64108
        • Truman Medical Center
      • Kansas City, Missouri, United States, 64118
        • Heartland Hematology and Oncology Associates Incorporated
      • Lee's Summit, Missouri, United States, 64086
        • Saint Luke's East - Lee's Summit
      • Saint Joseph, Missouri, United States, 64507
        • Heartland Regional Medical Center
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint Louis, Missouri, United States, 63141
        • Saint Louis-Cape Girardeau CCOP
      • Springfield, Missouri, United States, 65807
        • CoxHealth South Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Sunrise Hospital and Medical Center
      • Reno, Nevada, United States, 89502
        • Center of Hope at Renown Medical Center
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper Hospital University Medical Center
      • Mount Holly, New Jersey, United States, 08060
        • Virtua Memorial
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
    • New York
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Medical Center
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • North Carolina
      • Burlington, North Carolina, United States, 27215
        • Cone Health Cancer Center at Alamance Regional
      • Charlotte, North Carolina, United States, 28204
        • Novant Health Presbyterian Medical Center
      • Pinehurst, North Carolina, United States, 28374
        • FirstHealth of the Carolinas-Moore Regional Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45220
        • Good Samaritan Hospital - Cincinnati
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati/Barrett Cancer Center
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43222
        • Mount Carmel Health Center West
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Tulsa, Oklahoma, United States, 74146
        • Oklahoma Cancer Specialists and Research Institute-Tulsa
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Wynnewood, Pennsylvania, United States, 19096
        • Main Line Health NCORP
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Women and Infants Hospital
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Chattanooga's Program In Women's Oncology
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37208
        • Meharry Medical College
    • Texas
      • Amarillo, Texas, United States, 79106
        • The Don and Sybil Harrington Cancer Center
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
      • Roanoke, Virginia, United States, 24016
        • Carilion Clinic Gynecological Oncology
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • Saint Vincent Hospital Cancer Center Green Bay
      • West Allis, Wisconsin, United States, 53227
        • Aurora West Allis Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I (zoledroic acid)
Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Zoledronic Acid
Given IV
Other Names:
  • Reclast
  • Zometa
  • CGP 42446
  • CGP42446A
  • [1-Hydroxy-2-(1H-imidazol-1-yl)ethylidene]bisphosphonic Acid
  • NDC-Zoledronate
  • ZOL 446
No Intervention: Arm II (clinical observation)
Patients are observed for 18 months after surgery.

What is the study measuring?

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
Time Frame: 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
Time Frame: 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
Time Frame: 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
18 months
Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip
Time Frame: 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
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gynecologic Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: David S Alberts, Gynecologic Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 28, 2005

Primary Completion (Actual)

December 22, 2011

Study Registration Dates

First Submitted

March 21, 2006

First Submitted That Met QC Criteria

March 21, 2006

First Posted (Estimate)

March 22, 2006

Study Record Updates

Last Update Posted (Actual)

March 24, 2020

Last Update Submitted That Met QC Criteria

March 9, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GOG-0215 (Other Identifier: CTEP)
  • U10CA101165 (U.S. NIH Grant/Contract)
  • NCI-2009-00589 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • NCI-P6966
  • NOVARTIS-GOG-0215
  • CDR0000462217
  • NCI-06-C-0204

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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