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

Sponsor:	Radiation Therapy Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00329797

Purpose

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.

Condition	Intervention	Phase
Osteoporosis Prostate Cancer	Dietary Supplement: calcium carbonate Dietary Supplement: calcium citrate Dietary Supplement: calcium glucarate Dietary Supplement: cholecalciferol Drug: buserelin Drug: calcium gluconate Drug: goserelin Drug: leuprolide acetate Drug: triptorelin Drug: zoledronic acid Radiation: brachytherapy Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Supportive Care, Randomized
Official Title:	A Phase III Randomized Study to Evaluate the Efficacy of Zometa® for the Prevention of Osteoporosis and Associated Fractures in Patients Receiving Radiation Therapy and Long Term LHRH Agonists for High-Grade and/or Locally Advanced Prostate Cancer

Resource links provided by NLM:

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

Primary Outcome Measures:

Freedom from any bone fracture [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent change in bone mineral density at 3 years [ Designated as safety issue: No ]
Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General [ Designated as safety issue: No ]
Utility of the use of bisphosphonates as assessed by the European Questionnaire-5 Dimensional [ Designated as safety issue: No ]

Estimated Enrollment:	1272
Study Start Date:	March 2006
Estimated Primary Completion Date:	December 2020 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Parents receive zoledronate IV over 15 minutes once every 6 months. Patients also receive oral calcium and oral cholecaliciferol (vitamin D) once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.	Dietary Supplement: calcium carbonate Given orally Dietary Supplement: calcium citrate Given orally Dietary Supplement: calcium glucarate Given orally Dietary Supplement: cholecalciferol Given orally Drug: buserelin Given concurrently Drug: calcium gluconate Given orally Drug: goserelin Given concurrently Drug: leuprolide acetate Given concurrently Drug: triptorelin Given concurrently Drug: zoledronic acid Given IV Radiation: brachytherapy Given concurrently Radiation: radiation therapy Given concurrently
Arm II: Active Comparator Patients receive oral calcium and oral vitamin D once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.	Dietary Supplement: calcium carbonate Given orally Dietary Supplement: calcium citrate Given orally Dietary Supplement: calcium glucarate Given orally Dietary Supplement: cholecalciferol Given orally Drug: buserelin Given concurrently Drug: calcium gluconate Given orally Drug: goserelin Given concurrently Drug: leuprolide acetate Given concurrently Drug: triptorelin Given concurrently Radiation: brachytherapy Given concurrently Radiation: radiation therapy Given concurrently

Arms

Assigned Interventions

Arm I: Experimental

Parents receive zoledronate IV over 15 minutes once every 6 months. Patients also receive oral calcium and oral cholecaliciferol (vitamin D) once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.

Dietary Supplement: calcium carbonate

Given orally

Dietary Supplement: calcium citrate

Given orally

Dietary Supplement: calcium glucarate

Given orally

Dietary Supplement: cholecalciferol

Given orally

Drug: buserelin

Given concurrently

Drug: calcium gluconate

Given orally

Drug: goserelin

Given concurrently

Drug: leuprolide acetate

Given concurrently

Drug: triptorelin

Given concurrently

Drug: zoledronic acid

Given IV

Radiation: brachytherapy

Given concurrently

Radiation: radiation therapy

Given concurrently

Arm II: Active Comparator

Patients receive oral calcium and oral vitamin D once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity. Patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.

Dietary Supplement: calcium carbonate

Given orally

Dietary Supplement: calcium citrate

Given orally

Dietary Supplement: calcium glucarate

Given orally

Dietary Supplement: cholecalciferol

Given orally

Drug: buserelin

Given concurrently

Drug: calcium gluconate

Given orally

Drug: goserelin

Given concurrently

Drug: leuprolide acetate

Given concurrently

Drug: triptorelin

Given concurrently

Radiation: brachytherapy

Given concurrently

Radiation: radiation therapy

Given concurrently

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.

Arm I: Parents receive zoledronate IV over 15 minutes once every 6 months. Patients also receive oral calcium and oral cholecaliciferol (vitamin D) once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity.
Arm II: Patients receive oral calcium and oral vitamin D once daily. Treatment continues for 3 years in the absence of bone fractures, disease progression, or unacceptable toxicity.

All patients also undergo concurrent radiotherapy (external beam, brachytherapy, or both) and LHRH agonist (e.g., leuoprolide acetate, goserelin, buserelin, or triptorelin) therapy.

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

PROJECTED ACCRUAL: A total of 1,272 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed adenocarcinoma of the prostate
- Diagnosed within the past 12 months
Any 1 of the following clinical stages:
- Clinical stage T3, any N, M0 with any Gleason score and any prostate-specific antigen (PSA)
- Any T, any N, M0 with one of the following:
  - Gleason score ≥ 8 and any PSA
  - Gleason score 7 and PSA ≥ 15 ng/mL
  - Gleason score < 7 and PSA ≥ 20 ng/mL
Baseline T score > -2.5 in both the L spine and the total hip by dual x-ray absorptiometry (DXA) scan
Planning to receive luteinizing hormone-releasing hormone (LHRH) agonist therapy
- If patient is receiving LHRH therapy before study entry, therapy must have begun ≤ 6 months prior to study entry
- Scheduled to receive a LHRH agonist for ≥ 1 year
Planning to undergo radiotherapy (i.e., external-beam, brachytherapy, or both)
No distant metastases
- Must have negative bone scan for metastatic disease

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
Creatinine clearance > 30 mL/min
Calcium 8.4-10.6 mg/dL
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
No history of Paget's disease
No uncontrolled thyroid or parathyroid dysfunction
No known hypersensitivity to zoledronate or other bisphosphonates
No infection of the teeth or jawbone
No dental or fixture trauma
No current or prior diagnosis of osteonecrosis of the jaw
No exposed bone in the mouth
No slow healing after dental procedures
No other active dental problems
No other diseases that influence bone metabolism
No other malignancy within the past 3 years except nonmelanomatous skin cancer or carcinoma in situ of the breast or oral cavity

PRIOR CONCURRENT THERAPY:

See Disease Characterisitics
More than 6 weeks since prior dental or jaw surgery (e.g., extraction, implants)
No prior bisphosphonate therapy
No prior pelvic radiation
No prior systemic radiotherapeutic agents, such as strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
No concurrent systemic chemotherapy
No concurrent steroids
No concurrent growth hormones
No concurrent calcitonin
No concurrent dental or jaw surgery

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00329797

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Locations

United States, California
Enloe Cancer Center at Enloe Medical Center
Chico, California, United States, 95926
Radiation Oncology Center - Roseville
Roseville, California, United States, 95661
Radiological Associates of Sacramento Medical Group, Incorporated
Sacramento, California, United States, 95815
Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
Pomona, California, United States, 91767
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
United States, Colorado
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, United States, 80933
St. Mary - Corwin Regional Medical Center
Pueblo, Colorado, United States, 81004
United States, Georgia
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Northwest Community Hospital
Arlington Heights, Illinois, United States, 60005
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, United States, 62002
Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
Olympia Fields, Illinois, United States, 60461
United States, Indiana
Center for Cancer Care at Goshen General Hospital
Goshen, Indiana, United States, 46526
Methodist Cancer Center at Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States, 40536-0093
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
St. Agnes Hospital Cancer Center
Baltimore, Maryland, United States, 21229
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
United States, Minnesota
CentraCare Clinic - River Campus
Saint Cloud, Minnesota, United States, 56303
Coborn Cancer Center
Saint Cloud, Minnesota, United States, 56303
United States, Missouri
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
CCOP - St. Louis-Cape Girardeau
Saint Louis, Missouri, United States, 63141
David C. Pratt Cancer Center at St. John's Mercy
Saint Louis, Missouri, United States, 63141
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, United States, 65807
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
Cape Girardeau, Missouri, United States, 63701
St. John's Regional Health Center
Springfield, Missouri, United States, 65804
United States, Montana
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
Great Falls Clinic - Main Facility
Great Falls, Montana, United States, 59405
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
United States, Nevada
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
Renown Institute for Cancer at Renown Regional Medical Center
Reno, Nevada, United States, 89502
University Medical Center of Southern Nevada
Las Vegas, Nevada, United States, 89102
United States, New Hampshire
Kingsbury Center for Cancer Care at Cheshire Medical Center
Keene, New Hampshire, United States, 03431
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Cancer Institute of New Jersey at Cooper University Hospital - Camden
Camden, New Jersey, United States, 08103
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
Vineland, New Jersey, United States, 08360
United States, New York
CCOP - Hematology-Oncology Associates of Central New York
East Syracuse, New York, United States, 13057
Lourdes Regional Cancer Center
Binghamton, New York, United States, 13905
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Veterans Affairs Medical Center - Brooklyn
Brooklyn, New York, United States, 11209
United States, North Carolina
Cancer Centers of North Carolina - Raleigh
Raleigh, North Carolina, United States, 27607
Mission Hospitals - Memorial Campus
Asheville, North Carolina, United States, 28801
Wayne Radiation Oncology
Goldsboro, North Carolina, United States, 27534
Wilmed Radiation Oncology Services
Wilson, North Carolina, United States, 27893
United States, Ohio
Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
Salem, Ohio, United States, 44460
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, United States, 44309-2090
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, United States, 45267
McDowell Cancer Center at Akron General Medical Center
Akron, Ohio, United States, 44307
Precision Radiotherapy at University Pointe
West Chester, Ohio, United States, 45069
Cancer Treatment Center
Wooster, Ohio, United States, 44691
United States, Pennsylvania
Adams Cancer Center
Gettysburg, Pennsylvania, United States, 17325
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, United States, 19010
Cancer Center of Paoli Memorial Hospital
Paoli, Pennsylvania, United States, 19301-1792
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
Lankenau Cancer Center at Lankenau Hospital
Wynnewood, Pennsylvania, United States, 19096
Rosenfeld Cancer Center at Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
York Cancer Center at Apple Hill Medical Center
York, Pennsylvania, United States, 17405
United States, Tennessee
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
Kingsport, Tennessee, United States, 37662
United States, Utah
Dixie Regional Medical Center - East Campus
Saint George, Utah, United States, 84770
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
Murray, Utah, United States, 84157
LDS Hospital
Salt Lake City, Utah, United States, 84143
Utah Valley Regional Medical Center - Provo
Provo, Utah, United States, 84604
Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
United States, Vermont
Norris Cotton Cancer Center - North
Saint Johnsbury, Vermont, United States, 05819
United States, Virginia
Naval Medical Center - Portsmouth
Portsmouth, Virginia, United States, 23708-2197
Sentara Cancer Institute at Sentara Norfolk General Hospital
Norfolk, Virginia, United States, 23507
United States, Washington
North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
Yakima, Washington, United States, 98902
United States, Wisconsin
Theda Care Cancer Institute
Appleton, Wisconsin, United States, 54911
Community Memorial Hospital Cancer Care Center
Menomonee Falls, Wisconsin, United States, 53051
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, United States, 54143
Veterans Affairs Medical Center - Milwaukee
Milwaukee, Wisconsin, United States, 53295
Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
West Allis Memorial Hospital
West Allis, Wisconsin, United States, 53227
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Island Centre
Victoria, British Columbia, Canada, V8R 6V5
Canada, Newfoundland and Labrador
Doctor H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Cancer Care Program at Thunder Bay Regional Health Sciences
Thunder Bay, Ontario, Canada, P7B 6V4
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
Canada, Quebec
Centre Hospitalier Universitaire de Quebec
Quebec City, Quebec, Canada, G1R 2J6
CHUS-Hopital Fleurimont
Sherbrooke, Quebec, Canada, J1H 5N4
Maisonneuve-Rosemont Hospital
Montreal, Quebec, Canada, H1T 2M4
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Colleen A. Lawton, MD	Medical College of Wisconsin
Investigator:	Matthew R. Smith, MD	Massachusetts General Hospital
Investigator:	Margaret Chamberlain-Wilmoth, PhD, MSS, RN	Carolinas Medical Center - University

Responsible Party:	Radiation Therapy Oncology Group ( Walter John Curran, Jr )
Study ID Numbers:	CDR0000476469, RTOG-0518
Study First Received:	May 23, 2006
Last Updated:	May 27, 2009
ClinicalTrials.gov Identifier:	NCT00329797 History of Changes
Health Authority:	United States: Federal Government