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

Phase 2

Completed

• Conditions: Osteoporosis; Ovarian Carcinoma; Hereditary Breast and Ovarian Cancer Syndrome
• Interventions: Other: Laboratory Biomarker Analysis; Drug: Zoledronic Acid

• Registration Number: NCT00305695
• Lead Sponsor: Gynecologic Oncology Group

Brief 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.

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 Timeline

• Study Start: 2005-11-28
• Study First Submitted: 2006-03-21
• Study First Submitted QC: 2006-03-21
• Study First Posted: 2006-03-22
• Primary Completion: 2011-12-22
• Status Verified: 2020-03
• Results First Submitted: 2020-03-09
• Results First Submitted QC: 2020-03-09
• Last Update Submitted: 2020-03-09
• Results First Posted: 2020-03-24
• Last Update Posted: 2020-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 160

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (zoledroic acid)	Laboratory Biomarker Analysis	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.
Arm I (zoledroic acid)	Zoledronic Acid	Beginning 60-90 days after surgery, patients receive zoledronate IV over 15 minutes once in months 3, 9, and 15.

Primary Outcome Measures

Name	Time	Method
Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 9 Months	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).
Bone Mineral Density of the Lumbar Spine as Measured by Dual-energy X-ray Absorptiometry (DEXA) Scan at 18 Months	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).
Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Right Hip	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
Bone Mineral Density of the Total Hip as Measured by DEXA Scan on Left Hip	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

Trial Locations

Locations (95)

University of Illinois; 🇺🇸 Chicago, Illinois, United States

Indiana University/Melvin and Bren Simon Cancer Center; 🇺🇸 Indianapolis, Indiana, United States

University of California San Diego; 🇺🇸 San Diego, California, United States

University of Minnesota/Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States

University of Cincinnati/Barrett Cancer Center; 🇺🇸 Cincinnati, Ohio, United States

Virtua Memorial; 🇺🇸 Mount Holly, New Jersey, United States

FirstHealth of the Carolinas-Moore Regional Hospital; 🇺🇸 Pinehurst, North Carolina, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone; 🇺🇸 New York, New York, United States

Union Hospital of Cecil County; 🇺🇸 Elkton, Maryland, United States

Cooper Hospital University Medical Center; 🇺🇸 Camden, New Jersey, United States

Case Western Reserve University; 🇺🇸 Cleveland, Ohio, United States

Good Samaritan Hospital - Cincinnati; 🇺🇸 Cincinnati, Ohio, United States

Saint Luke's East - Lee's Summit; 🇺🇸 Lee's Summit, Missouri, United States

North Shore University Hospital; 🇺🇸 Manhasset, New York, United States

MedStar Franklin Square Medical Center/Weinberg Cancer Institute; 🇺🇸 Baltimore, Maryland, United States

Riverside Methodist Hospital; 🇺🇸 Columbus, Ohio, United States

Novant Health Presbyterian Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Mercy Hospital Saint Louis; 🇺🇸 Saint Louis, Missouri, United States

Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Main Line Health NCORP; 🇺🇸 Wynnewood, Pennsylvania, United States

Carilion Clinic Gynecological Oncology; 🇺🇸 Roanoke, Virginia, United States

William Beaumont Hospital-Royal Oak; 🇺🇸 Royal Oak, Michigan, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States

Sunrise Hospital and Medical Center; 🇺🇸 Las Vegas, Nevada, United States

Baptist Health Lexington; 🇺🇸 Lexington, Kentucky, United States

Mount Sinai Hospital; 🇺🇸 New York, New York, United States

Saint Louis-Cape Girardeau CCOP; 🇺🇸 Saint Louis, Missouri, United States

Cone Health Cancer Center at Alamance Regional; 🇺🇸 Burlington, North Carolina, United States

Saint Vincent Hospital Cancer Center Green Bay; 🇺🇸 Green Bay, Wisconsin, United States

West Michigan Cancer Center; 🇺🇸 Kalamazoo, Michigan, United States

University of Vermont Medical Center; 🇺🇸 Burlington, Vermont, United States

Mount Carmel Health Center West; 🇺🇸 Columbus, Ohio, United States

University of Virginia Cancer Center; 🇺🇸 Charlottesville, Virginia, United States

University of New Mexico Cancer Center; 🇺🇸 Albuquerque, New Mexico, United States

CoxHealth South Hospital; 🇺🇸 Springfield, Missouri, United States

Women and Infants Hospital; 🇺🇸 Providence, Rhode Island, United States

The Don and Sybil Harrington Cancer Center; 🇺🇸 Amarillo, Texas, United States

Menorah Medical Center; 🇺🇸 Overland Park, Kansas, United States

Saint Luke's South Hospital; 🇺🇸 Overland Park, Kansas, United States

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Vanderbilt University/Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Meharry Medical College; 🇺🇸 Nashville, Tennessee, United States

SCL Health Saint Joseph Hospital; 🇺🇸 Denver, Colorado, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Heartland Regional Medical Center; 🇺🇸 Saint Joseph, Missouri, United States

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center; 🇺🇸 Burbank, California, United States

University of Arizona Cancer Center-North Campus; 🇺🇸 Tucson, Arizona, United States

Kaiser Permanente Los Angeles Medical Center; 🇺🇸 Los Angeles, California, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Stanford Cancer Institute Palo Alto; 🇺🇸 Palo Alto, California, United States

UC Irvine Health/Chao Family Comprehensive Cancer Center; 🇺🇸 Orange, California, United States

Boulder Community Hospital; 🇺🇸 Boulder, Colorado, United States

Penrose-Saint Francis Healthcare; 🇺🇸 Colorado Springs, Colorado, United States

Rose Medical Center; 🇺🇸 Denver, Colorado, United States

North Colorado Medical Center; 🇺🇸 Greeley, Colorado, United States

The Hospital of Central Connecticut; 🇺🇸 New Britain, Connecticut, United States

McKee Medical Center; 🇺🇸 Loveland, Colorado, United States

SCL Health Lutheran Medical Center; 🇺🇸 Wheat Ridge, Colorado, United States

Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital; 🇺🇸 Newark, Delaware, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Jupiter Medical Center; 🇺🇸 Jupiter, Florida, United States

Tripler Army Medical Center; 🇺🇸 Honolulu, Hawaii, United States

Carle Cancer Center; 🇺🇸 Urbana, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital; 🇺🇸 Evanston, Illinois, United States

Northwestern Medicine Central DuPage Hospital; 🇺🇸 Winfield, Illinois, United States

Saint Vincent Hospital and Health Care Center; 🇺🇸 Indianapolis, Indiana, United States

Memorial Hospital of South Bend; 🇺🇸 South Bend, Indiana, United States

University of Iowa/Holden Comprehensive Cancer Center; 🇺🇸 Iowa City, Iowa, United States

Mercy Hospital Springfield; 🇺🇸 Springfield, Missouri, United States

Long Island Jewish Medical Center; 🇺🇸 New Hyde Park, New York, United States

Northwell Health/Center for Advanced Medicine; 🇺🇸 Lake Success, New York, United States

UH Seidman Cancer Center at Lake Health Mentor Campus; 🇺🇸 Mentor, Ohio, United States

Oklahoma Cancer Specialists and Research Institute-Tulsa; 🇺🇸 Tulsa, Oklahoma, United States

Aurora West Allis Medical Center; 🇺🇸 West Allis, Wisconsin, United States

Holy Cross Hospital; 🇺🇸 Fort Lauderdale, Florida, United States

Banner University Medical Center - Tucson; 🇺🇸 Tucson, Arizona, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

North Suburban Medical Center; 🇺🇸 Thornton, Colorado, United States

Chattanooga's Program in Women's Oncology; 🇺🇸 Chattanooga, Tennessee, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Center of Hope at Renown Medical Center; 🇺🇸 Reno, Nevada, United States

University of California Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

Colorado Gynecologic Oncology Group; 🇺🇸 Aurora, Colorado, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

UF Cancer Center at Orlando Health; 🇺🇸 Orlando, Florida, United States

Norton Hospital Pavilion and Medical Campus; 🇺🇸 Louisville, Kentucky, United States

Saint Luke's Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Research Medical Center; 🇺🇸 Kansas City, Missouri, United States

Truman Medical Center; 🇺🇸 Kansas City, Missouri, United States

North Kansas City Hospital; 🇺🇸 Kansas City, Missouri, United States

Heartland Hematology and Oncology Associates Incorporated; 🇺🇸 Kansas City, Missouri, United States

Virginia Commonwealth University/Massey Cancer Center; 🇺🇸 Richmond, Virginia, United States