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Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy

Phase 3
Completed
Conditions
Osteoporosis
Prostate Cancer
Interventions
Dietary Supplement: Calcium
Radiation: radiation therapy
Dietary Supplement: Zoledronic acid
Drug: LHRH
Dietary Supplement: Vitamin D
Registration Number
NCT00329797
Lead Sponsor
Radiation Therapy Oncology Group
Brief Summary

RATIONALE: Zoledronate may prevent bone loss in patients with prostate cancer undergoing radiation therapy and hormone therapy. It is not yet known whether zoledronate is more effective than calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with locally advanced nonmetastatic prostate cancer undergoing radiation therapy and hormone therapy.

Detailed Description

OBJECTIVES:

Primary

* Compare the potential benefit of bisphosphonate therapy comprising zoledronate plus vitamin D and calcium supplement vs standard therapy with vitamin D and calcium supplement in the prevention of osteoporosis and associated bone fractures in patients with locally advanced nonmetastatic adenocarcinoma of the prostate undergoing radiotherapy and luteinizing hormone-releasing hormone (LHRH) agonist therapy.

Secondary

* Evaluate the potential benefit of these regimens on quality of life in these patients.

* Evaluate the potential benefit in bone mineral density over a period of 3 years for patients treated with these regimens.

OUTLINE: This is randomized multicenter study. Patients are stratified according to T score of the hip by dual x-ray absorptiometry (DXA) scan (\< -1.0 but \> -2.5 vs ≥ - 1.0) and planned duration of luteinizing hormone-releasing hormone (LHRH) agonist therapy (1-2½ years vs \> 2½ years). Patients are randomized to 1 of 2 treatment arms.

Quality of life is assessed at baseline and every 6 months during treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
109
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Zoledronic AcidVitamin DZoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.
ControlLHRHVitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Zoledronic AcidLHRHZoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Controlradiation therapyVitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
ControlVitamin DVitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Zoledronic AcidCalciumZoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Zoledronic AcidZoledronic acidZoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Zoledronic Acidradiation therapyZoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.
ControlCalciumVitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
Primary Outcome Measures
NameTimeMethod
Freedom From Any Bone Fracture (FABF) Rate at Three YearsFrom randomization to 3 years

The time of failure was measured from the date of randomization to the date of documented bone fractures, defined as any fracture of the bone. The three-year FABF rate will be estimated by the Kaplan-Meier method.

Secondary Outcome Measures
NameTimeMethod
Percent Change in Bone Mineral Density at 3 YearsBaseline, 3 years from start of treatment

Bone mineral density (BMD) was measured by DXA scan (Dual X-ray absorptiometry) for five locations: lumbar, right total hip, left total hip, right femoral neck, and left femoral neck. The percent change at 3 years was calculated for each location by the following formula: Percent Change BMD = (BMD_3 years - BMD_Baseline)/ BMD_Baseline \* 100.

Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 YearsBaseline, 3 years from start of treatment

The FACT-G is a validated, 27-item measure. In addition to a total QOL score, subscale scores for physical, functional, social and emotional well-being are produced. There are 5 responses options, with 0=Not a lot and 4=Very much. All items in a subscale are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Scores range from 0-108 for the FACT-G total score, 0-28 for the physical, social and functional subscales, and 0-24 for the emotional subscale. Certain items, identified on the FACT-G scoring guides, must be reversed before it is added by subtracting the response from 4. All subscale totals are added together to form the FACT-G total score. Each subscale requires at least 50% of the items to be completed while the overall response rate must be greater than 80%. If items are missing, the subscale scores can be prorated. A higher score indicates better QOL.

Utility of the Use of Bisphosphonates as Assessed by Quality-adjusted SurvivalFrom pre-treatment to 3 years from start of treatment

The EQ-5D is a standardized instrument for measuring generic health status used to generate health utilities, used to derive quality adjusted survival. Quality adjusted survival is computed using the weighted sum of times in different health states added up to a total quality-adjusted survival time. The log-rank test is used to compare quality-adjusted survivals between the treatment arms.

Trial Locations

Locations (88)

USC/Norris Comprehensive Cancer Center and Hospital

🇺🇸

Los Angeles, California, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

University Medical Center of Southern Nevada

🇺🇸

Las Vegas, Nevada, United States

CCOP - Nevada Cancer Research Foundation

🇺🇸

Las Vegas, Nevada, United States

LDS Hospital

🇺🇸

Salt Lake City, Utah, United States

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

CCOP - Montana Cancer Consortium

🇺🇸

Billings, Montana, United States

Radiation Oncology Center - Roseville

🇺🇸

Roseville, California, United States

CentraCare Clinic - River Campus

🇺🇸

Saint Cloud, Minnesota, United States

Northeast Georgia Medical Center

🇺🇸

Gainesville, Georgia, United States

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital

🇺🇸

Cape Girardeau, Missouri, United States

Coborn Cancer Center

🇺🇸

Saint Cloud, Minnesota, United States

Penrose Cancer Center at Penrose Hospital

🇺🇸

Colorado Springs, Colorado, United States

Methodist Cancer Center at Methodist Hospital

🇺🇸

Indianapolis, Indiana, United States

Saint Anthony's Hospital at Saint Anthony's Health Center

🇺🇸

Alton, Illinois, United States

CCOP - St. Louis-Cape Girardeau

🇺🇸

Saint Louis, Missouri, United States

Lourdes Regional Cancer Center

🇺🇸

Binghamton, New York, United States

St. Mary - Corwin Regional Medical Center

🇺🇸

Pueblo, Colorado, United States

Northern Rockies Radiation Oncology Center

🇺🇸

Billings, Montana, United States

Josephine Ford Cancer Center at Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Wayne Radiation Oncology

🇺🇸

Goldsboro, North Carolina, United States

Northwest Community Hospital

🇺🇸

Arlington Heights, Illinois, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

🇺🇸

Saint Louis, Missouri, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Ingalls Cancer Care Center at Ingalls Memorial Hospital

🇺🇸

Harvey, Illinois, United States

Veterans Affairs Medical Center - Brooklyn

🇺🇸

Brooklyn, New York, United States

Wilmed Radiation Oncology Services

🇺🇸

Wilson, North Carolina, United States

Bryn Mawr Hospital

🇺🇸

Bryn Mawr, Pennsylvania, United States

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

🇺🇸

Murray, Utah, United States

Utah Valley Regional Medical Center - Provo

🇺🇸

Provo, Utah, United States

Precision Radiotherapy at University Pointe

🇺🇸

West Chester, Ohio, United States

Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford

🇺🇸

Salem, Ohio, United States

Cancer Center of Paoli Memorial Hospital

🇺🇸

Paoli, Pennsylvania, United States

Fox Chase Cancer Center - Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Norris Cotton Cancer Center - North

🇺🇸

Saint Johnsbury, Vermont, United States

Sentara Cancer Institute at Sentara Norfolk General Hospital

🇺🇸

Norfolk, Virginia, United States

Bay Area Cancer Care Center at Bay Area Medical Center

🇺🇸

Marinette, Wisconsin, United States

Community Memorial Hospital Cancer Care Center

🇺🇸

Menomonee Falls, Wisconsin, United States

British Columbia Cancer Agency - Vancouver Island Centre

🇨🇦

Victoria, British Columbia, Canada

Centre Hospitalier Universitaire de Quebec

🇨🇦

Quebec City, Quebec, Canada

Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center

🇺🇸

Milwaukee, Wisconsin, United States

Medical College of Wisconsin Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

Veterans Affairs Medical Center - Milwaukee

🇺🇸

Milwaukee, Wisconsin, United States

Rosenfeld Cancer Center at Abington Memorial Hospital

🇺🇸

Abington, Pennsylvania, United States

CCOP - Hematology-Oncology Associates of Central New York

🇺🇸

East Syracuse, New York, United States

McDowell Cancer Center at Akron General Medical Center

🇺🇸

Akron, Ohio, United States

Summa Center for Cancer Care at Akron City Hospital

🇺🇸

Akron, Ohio, United States

Cancer Treatment Center

🇺🇸

Wooster, Ohio, United States

Lankenau Cancer Center at Lankenau Hospital

🇺🇸

Wynnewood, Pennsylvania, United States

Adams Cancer Center

🇺🇸

Gettysburg, Pennsylvania, United States

David C. Pratt Cancer Center at St. John's Mercy

🇺🇸

Saint Louis, Missouri, United States

St. John's Regional Health Center

🇺🇸

Springfield, Missouri, United States

Hulston Cancer Center at Cox Medical Center South

🇺🇸

Springfield, Missouri, United States

Theda Care Cancer Institute

🇺🇸

Appleton, Wisconsin, United States

Charles M. Barrett Cancer Center at University Hospital

🇺🇸

Cincinnati, Ohio, United States

Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields

🇺🇸

Olympia Fields, Illinois, United States

Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center

🇺🇸

Pomona, California, United States

Enloe Cancer Center at Enloe Medical Center

🇺🇸

Chico, California, United States

Lucille P. Markey Cancer Center at University of Kentucky

🇺🇸

Lexington, Kentucky, United States

Center for Cancer Care at Goshen General Hospital

🇺🇸

Goshen, Indiana, United States

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

🇺🇸

Yakima, Washington, United States

Cancer Care Program at Thunder Bay Regional Health Sciences

🇨🇦

Thunder Bay, Ontario, Canada

Maisonneuve-Rosemont Hospital

🇨🇦

Montreal, Quebec, Canada

York Cancer Center at Apple Hill Medical Center

🇺🇸

York, Pennsylvania, United States

West Allis Memorial Hospital

🇺🇸

West Allis, Wisconsin, United States

Renown Institute for Cancer at Renown Regional Medical Center

🇺🇸

Reno, Nevada, United States

Cancer Institute of New Jersey at Cooper - Voorhees

🇺🇸

Voorhees, New Jersey, United States

Mission Hospitals - Memorial Campus

🇺🇸

Asheville, North Carolina, United States

Val and Ann Browning Cancer Center at McKay-Dee Hospital Center

🇺🇸

Ogden, Utah, United States

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center

🇺🇸

Kingsport, Tennessee, United States

Naval Medical Center - Portsmouth

🇺🇸

Portsmouth, Virginia, United States

Cancer Centers of North Carolina - Raleigh

🇺🇸

Raleigh, North Carolina, United States

CCOP - Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Radiological Associates of Sacramento Medical Group, Incorporated

🇺🇸

Sacramento, California, United States

CCOP - Kansas City

🇺🇸

Kansas City, Missouri, United States

St. Agnes Hospital Cancer Center

🇺🇸

Baltimore, Maryland, United States

West Michigan Cancer Center

🇺🇸

Kalamazoo, Michigan, United States

Kingsbury Center for Cancer Care at Cheshire Medical Center

🇺🇸

Keene, New Hampshire, United States

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

St. Vincent Hospital Regional Cancer Center

🇺🇸

Green Bay, Wisconsin, United States

Great Falls Clinic - Main Facility

🇺🇸

Great Falls, Montana, United States

CHUS-Hopital Fleurimont

🇨🇦

Sherbrooke, Quebec, Canada

Cancer Institute of New Jersey at Cooper University Hospital - Camden

🇺🇸

Camden, New Jersey, United States

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

🇺🇸

Vineland, New Jersey, United States

Dixie Regional Medical Center - East Campus

🇺🇸

Saint George, Utah, United States

Doctor H. Bliss Murphy Cancer Centre

🇨🇦

St. John's, Newfoundland and Labrador, Canada

Margaret and Charles Juravinski Cancer Centre

🇨🇦

Hamilton, Ontario, Canada

Allan Blair Cancer Centre at Pasqua Hospital

🇨🇦

Regina, Saskatchewan, Canada

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