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

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00305695
• Other study ID #: GOG-0215
• Secondary ID: NCI-2009-00589NC
• Status: Completed
• Phase: Phase 2
• Start date: November 28, 2005

Study information

• Verified date: March 2020
• Source: Gynecologic Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 160
• Est. primary completion date: December 22, 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Hereditary Breast and Ovarian Cancer Syndrome
• Osteoporosis
• Ovarian Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Zoledronic Acid
Given IV

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Colorado Gynecologic Oncology Group	Aurora	Colorado
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Boulder Community Hospital	Boulder	Colorado
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Chattanooga's Program in Women's Oncology	Chattanooga	Tennessee
United States	University of Illinois	Chicago	Illinois
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Rose Medical Center	Denver	Colorado
United States	SCL Health Saint Joseph Hospital	Denver	Colorado
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	North Colorado Medical Center	Greeley	Colorado
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Hartford Hospital	Hartford	Connecticut
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Jupiter Medical Center	Jupiter	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Center	Kansas City	Missouri
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Norton Hospital Pavilion and Medical Campus	Louisville	Kentucky
United States	McKee Medical Center	Loveland	Colorado
United States	North Shore University Hospital	Manhasset	New York
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Meharry Medical College	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Oregon Health and Science University	Portland	Oregon
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Center of Hope at Renown Medical Center	Reno	Nevada
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	University of California San Diego	San Diego	California
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	North Suburban Medical Center	Thornton	Colorado
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Carle Cancer Center	Urbana	Illinois
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado
United States	Northwestern Medicine Central DuPage Hospital	Winfield	Illinois
United States	Main Line Health NCORP	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Gynecologic Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 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
Primary	Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 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
Primary	Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Right Hip	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
Primary	Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip	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