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

Condition(s) targeted: Cancer-Related Problem/Condition; Prostate Cancer

Intervention: buserelin (Drug); calcium carbonate (Drug); calcium citrate (Drug); calcium glucarate (Drug); calcium gluconate (Drug); cholecalciferol (Drug); goserelin (Drug); leuprolide acetate (Drug); triptorelin (Drug); zoledronic acid (Drug); brachytherapy (Procedure); radiation therapy (Procedure)

Phase: Phase 3

Status: Recruiting

Sponsored by: Radiation Therapy Oncology Group

Official(s) and/or principal investigator(s):
Colleen A. Lawton, MD, Study Chair, Affiliation: Medical College of Wisconsin
Matthew R. Smith, MD, Affiliation: Massachusetts General Hospital
Margaret Chamberlain-Wilmoth, PhD, MSS, RN, Affiliation: Carolinas Medical Center - University

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.

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

Study design: Supportive Care, Randomized, Double-Blind

Primary outcome: Freedom from any bone fracture

Secondary outcome:

Percent change in bone mineral density at 3 years

Changes in quality of life as assessed by the Functional Assessment of Cancer Therapy-General

Utility of the use of bisphosphonates as assessed by the European Questionnaire-5 Dimensional

Detailed description: OBJECTIVES:

Primary

- Compare the potential benefit of bisphosphonate therapy comprising zoledronate vs

standard therapy with vitamin D and calcium suppliment 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

- Compare the potential benefit of these regimens on quality of life in these patients.

- Compare the differences in bone mineral density over a period of 3 years in patients

treated with these regimens.

OUTLINE: This is randomized, double-blind, 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the prostate

- Diagnosed within the past 6 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

- Any Gleason score and PSA ≥ 30 ng/mL

- Gleason score ≥ 7 and PSA ≥ 15 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

≤ 12 weeks 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 < 1. 4 mg/dL

- Creatinine clearance > 60 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

Tom Baker Cancer Centre - Calgary, Calgary, Alberta T2N 4N2, Canada; Recruiting
Alexander G. Balogh, Phone: 403-521-3701

British Columbia Cancer Agency - Vancouver Island Centre, Victoria, British Columbia V8R 6V5, Canada; Recruiting
Abraham S. Alexander, Phone: 250-519-5500

Enloe Cancer Center at Enloe Medical Center, Chico, California 95926, United States; Recruiting
Clinical Trials Office - Enloe Cancer Center at Enloe Medical, Phone: 530-332-3808

Radiation Oncology Center - Roseville, Roseville, California 95661, United States; Recruiting
Christopher Jones, MD, Phone: 916-969-4422

Radiological Associates of Sacramento Medical Group, Incorporated, Sacramento, California 95815, United States; Recruiting
Christopher Jones, MD, Phone: 916-646-8300

Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center, Pomona, California 91767, United States; Recruiting
Clinical Trials Office - Robert and Beverly Lewis Family Cance, Phone: 909-865-9555

USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles, California 90089-9181, United States; Recruiting
Clinical Trials Office - USC/Norris Comprehensive Cancer Cente, Phone: 323-865-0451

Penrose Cancer Center at Penrose Hospital, Colorado Springs, Colorado 80933, United States; Recruiting
Clinical Trials Office - Penrose Cancer Center, Phone: 719-776-5275

St. Mary - Corwin Regional Medical Center, Pueblo, Colorado 81004, United States; Recruiting
John D. Stageberg, Phone: 719-557-4000

Northeast Georgia Medical Center, Gainesville, Georgia 30501, United States; Recruiting
Frank G. Lake, MD, Phone: 770-535-3393

CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States; Recruiting
Clinical Trials Office - CCOP - Carle Cancer Center, Phone: 800-446-5532

Ingalls Cancer Care Center at Ingalls Memorial Hospital, Harvey, Illinois 60426, United States; Recruiting
Clinical Trials Office - Ingalls Cancer Care Center at Ingalls, Phone: 708-915-6747

Northwest Community Hospital, Arlington Heights, Illinois 60005, United States; Recruiting
Stephen S. Nigh, MD, Phone: 847-618-6560

Saint Anthony's Hospital at Saint Anthony's Health Center, Alton, Illinois 62002, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-6573

Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields, Olympia Fields, Illinois 60461, United States; Recruiting
Clinical Trials Office - Saint James Hospital and Health Cent, Phone: 708-679-2217

Center for Cancer Care at Goshen General Hospital, Goshen, Indiana 46526, United States; Recruiting
Clinical Trials Office - Center for Cancer Care at Goshen Gene, Phone: 574-535-2858

Methodist Cancer Center at Methodist Hospital, Indianapolis, Indiana 46202, United States; Recruiting
Contact Person, Phone: 317-962-8288

Saint John's Cancer Center at Saint John's Medical Center, Anderson, Indiana 46016, United States; Recruiting
Darrel L. Ross, Phone: 765-646-8459

Lucille P. Markey Cancer Center at University of Kentucky, Lexington, Kentucky 40536-0093, United States; Recruiting
Clinical Trials Office - Markey Cancer Center at University of, Phone: 859-257-3379

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States; Recruiting
Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce, Phone: 410-955-8804, Email: jhcccro@jhmi.edu

St. Agnes Hospital Cancer Center, Baltimore, Maryland 21229, United States; Recruiting
Richard S. Hudes, MD, Phone: 410-368-2910

Barbara Ann Karmanos Cancer Institute, Detroit, Michigan 48201-1379, United States; Recruiting
Clinical Trials Office - Barbara Ann Karmanos Cancer Institute, Phone: 313-576-9363

Josephine Ford Cancer Center at Henry Ford Hospital, Detroit, Michigan 48202, United States; Recruiting
Eleanor M. Walker, MD, Phone: 313-916-1850

West Michigan Cancer Center, Kalamazoo, Michigan 49007-3731, United States; Recruiting
Clinical Trials Office - West Michigan Cancer Center, Phone: 269-373-7458

CentraCare Clinic - River Campus, Saint Cloud, Minnesota 56303, United States; Recruiting
Barbi L. Kaplan-Frenkel, DO, Phone: 320-252-5131

Coborn Cancer Center, Saint Cloud, Minnesota 56303, United States; Recruiting
Barbi L. Kaplan-Frenkel, DO, Phone: 320-229-4907

CCOP - Kansas City, Kansas City, Missouri 64131, United States; Recruiting
Rakesh Gaur, MD, Phone: 816-823-0555

CCOP - St. Louis-Cape Girardeau, Saint Louis, Missouri 63141, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-6573

David C. Pratt Cancer Center at St. John's Mercy, Saint Louis, Missouri 63141, United States; Recruiting
Clinical Trials Office - David C. Pratt Cancer Center at St. J, Phone: 314-251-6770

Hulston Cancer Center at Cox Medical Center South, Springfield, Missouri 65807, United States; Recruiting
John W. Goodwin, MD, Phone: 417-889-8099

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, Saint Louis, Missouri 63110, United States; Recruiting
Jeff M. Michalski, MD, Phone: 314-362-8566

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital, Gape Girardeau, Missouri 63701, United States; Recruiting
Bethany G. Sleckman, MD, Phone: 314-251-6573

St. John's Regional Health Center, Springfield, Missouri 65804, United States; Recruiting
John W. Goodwin, MD, Phone: 417-889-8099

CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-259-2245

Great Falls Clinic - Main Facility, Great Falls, Montana 59405, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-454-2171

Northern Rockies Radiation Oncology Center, Billings, Montana 59101, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 406-248-2212

CCOP - Nevada Cancer Research Foundation, Las Vegas, Nevada 89106, United States; Recruiting
John A. Ellerton, MD, CM, Phone: 702-384-0013

Renown Institute for Cancer at Renown Regional Medical Center, Reno, Nevada 89502, United States; Recruiting
Lawrence R. Dardick, MD, Phone: 775-982-5638

University Medical Center of Southern Nevada, Las Vegas, Nevada 89102, United States; Recruiting
John A. Ellerton, MD, CM, Phone: 702-383-2000

Kingsbury Center for Cancer Care at Cheshire Medical Center, Keene, New Hampshire 03431, United States; Recruiting
Alan C. Hartford, MD, PhD, Phone: 603-354-5400

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756-0002, United States; Recruiting
Clinical Trials Office - Norris Cotton Cancer Center, Phone: 603-650-7609, Email: cancerhelp@dartmouth.edu

Cancer Institute of New Jersey at Cooper University Hospital - Camden, Camden, New Jersey 08103, United States; Recruiting
Clinical Trial Office - Cancer Institute of New Jersey at Coop, Phone: 856-325-6757

Cancer Institute of New Jersey at Cooper - Voorhees, Voorhees, New Jersey 08043, United States; Recruiting
Clinical Trials Office - Cancer Institute of New Jersey at Coo, Phone: 856-325-6757

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare, Vineland, New Jersey 08360, United States; Recruiting
Clinical Trials Office - Franklin & Edith Scarpa Regional Canc, Phone: 856-641-7933

Lovelace Medical Center - Downtown, Albuquerque, New Mexico 87102, United States; Recruiting
Benny J. Liem, MD, Phone: 505-727-8000

CCOP - Hematology-Oncology Associates of Central New York, East Syracuse, New York 13057, United States; Recruiting
Jeffrey J. Kirshner, MD, Phone: 315-472-7504

Lourdes Regional Cancer Center, Binghamton, New York 13905, United States; Recruiting
Michael Fallon, Phone: 607-798-5230

Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States; Recruiting
Clinical Trials Office - Roswell Park Cancer Institute, Phone: 877-275-7724

Veterans Affairs Medical Center - Brooklyn, Brooklyn, New York 11209, United States; Recruiting
David Lawrence Schwartz, MD, Phone: 718-630-3574

Doctor H. Bliss Murphy Cancer Centre, St. John's, Newfoundland and Labrador A1B 3V6, Canada; Recruiting
Jonathan D. Greenland, Phone: 709-777-7589

Cancer Centers of North Carolina - Raleigh, Raleigh, North Carolina 27607, United States; Recruiting
John F. Reilly, Phone: 919-781-7070

Mission Hospitals - Memorial Campus, Asheville, North Carolina 28801, United States; Recruiting
Clinical Trials Office - Mission Hospitals - Memorial Campus, Phone: 828-213-4150

Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford, Salem, Ohio 44460, United States; Recruiting
William F. Demas, MD, Phone: 330-375-3557

Cancer Treatment Center, Wooster, Ohio 44691, United States; Recruiting
Clinical Trials Office - Cancer Treatment Center, Phone: 330-375-4221

Charles M. Barrett Cancer Center at University Hospital, Cincinnati, Ohio 45267, United States; Recruiting
Kevin P. Redmond, MD, Phone: 513-584-9089

Precision Radiotherapy at University Pointe, West Chester, Ohio 45069, United States; Recruiting
Kevin P. Redmond, MD, Phone: 513-584-9089

Summa Center for Cancer Care at Akron City Hospital, Akron, Ohio 44309-2090, United States; Recruiting
Clinical Trials Office - Akron City Hospital, Phone: 330-375-6101

Cancer Care Program at Thunder Bay Regional Health Sciences, Thunder Bay, Ontario P7B 6V4, Canada; Recruiting
Sunil Premial P. Gulavita, Phone: 807-684-7200

Adams Cancer Center, Gettysburg, Pennsylvania 17325, United States; Recruiting
Amit B. Shah, Phone: 717-741-8180

Bryn Mawr Hospital, Bryn Mawr, Pennsylvania 19010, United States; Recruiting
Clinical Trials Office - Bryn Mawr Hospital, Phone: 610-645-2680

Cancer Center of Paoli Memorial Hospital, Paoli, Pennsylvania 19301-1792, United States; Recruiting
Clinical Trials Office - Cancer Center of Paoli Memorial Hospi, Phone: 610-648-1637

Fox Chase Cancer Center - Philadelphia, Philadelphia, Pennsylvania 19111-2497, United States; Recruiting
Clinical Trials Office - Fox Chase Cancer Center - Philadelphi, Phone: 215-728-4790

Lankenau Cancer Center at Lankenau Hospital, Wynnewood, Pennsylvania 19096, United States; Recruiting
Paul B. Gilman, MD, Phone: 610-645-2000

Rosenfeld Cancer Center at Abington Memorial Hospital, Abington, Pennsylvania 19001, United States; Recruiting
Clinical Trials Office - Rosenfeld Cancer Center at Abington M, Phone: 215-481-2402

York Cancer Center at Apple Hill Medical Center, York, Pennsylvania 17405, United States; Recruiting
Amit B. Shah, Phone: 717-741-8180

Centre Hospitalier Universitaire de Quebec, Quebec City, Quebec G1R 2J6, Canada; Recruiting
Andre-Guy Martin, Phone: 418-525-4444

CHUS-Hopital Fleurimont, Sherbrooke, Quebec J1H 5N4, Canada; Recruiting
Abdenour Nabid, MD, FRCPC, Phone: 819-346-1110

Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; Recruiting
Nader Khaouam, Phone: 514-252-3400

Allan Blair Cancer Centre at Pasqua Hospital, Regina, Saskatchewan S4T 7T1, Canada; Recruiting
Evgeny Sadikov, Phone: 306-766-2203

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center, Kingsport, Tennessee 37662, United States; Recruiting
Clinical Trials Office - Christine LaGuardia Phillips Cancer C, Phone: 423-224-5593

Dixie Regional Medical Center - East Campus, Saint George, Utah 84770, United States; Recruiting
Clinical Trials Office - Dixie Regional Medical Center - East, Phone: 435-688-4167

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center, Murray, Utah 84157, United States; Recruiting
R. Jeffrey Lee, MD, Phone: 801-408-1146

LDS Hospital, Salt Lake City, Utah 84143, United States; Recruiting
R. Jeffrey Lee, MD, Phone: 801-408-1146

Utah Valley Regional Medical Center - Provo, Provo, Utah 84604, United States; Recruiting
Clinical Trials Office - Utah Valley Regional Medical Center -, Phone: 801-357-7965

Val and Ann Browning Cancer Center at McKay-Dee Hospital Center, Ogden, Utah 84403, United States; Recruiting
Clinical Trials Office - McKay-Dee Hospital Center, Phone: 801-387-7426

Norris Cotton Cancer Center - North, Saint Johnsbury, Vermont 05819, United States; Recruiting
Alan C. Hartford, MD, PhD, Phone: 802-473-4100

Naval Medical Center - Portsmouth, Portsmouth, Virginia 23708-2197, United States; Recruiting
Clinical Trials Office - Naval Medical Center - Portsmouth, Phone: 757-953-5939

Sentara Cancer Institute at Sentara Norfolk General Hospital, Norfolk, Virginia 23507, United States; Recruiting
Clinical Trials Office - Sentara Cancer Institute at Sentara N, Phone: 757-388-2406

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital, Yakima, Washington 98902, United States; Recruiting
Clinical Trails Office - North Star Lodge Cancer Center, Phone: 509-574-3422

Bay Area Cancer Care Center at Bay Area Medical Center, Marinette, Wisconsin 54143, United States; Recruiting
Gregory M. Cooley, MD, Phone: 414-433-8184

Community Memorial Hospital Cancer Care Center, Menomonee Falls, Wisconsin 53051, United States; Recruiting
Colleen A. Lawton, MD, Phone: 414-805-4472

Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin 53226, United States; Recruiting
Clinical Trials Office - Medical College of Wisconsin Cancer C, Phone: 414-805-4380

St. Vincent Hospital Regional Cancer Center, Green Bay, Wisconsin 54307-3508, United States; Recruiting
Clinical Trials Office - St. Vincent Hospital Regional Cancer, Phone: 920-433-8889

Theda Care Cancer Institute, Appleton, Wisconsin 54911, United States; Recruiting
Clinical Trials Office - Theda Care Cancer Institute, Phone: 920-380-1500

Veterans Affairs Medical Center - Milwaukee, Milwaukee, Wisconsin 53295, United States; Recruiting
Elizabeth M. Gore, MD, Phone: 414-805-4465

Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center, Milwaukee, Wisconsin 53215, United States; Recruiting
Clinical Trials Office - Vince Lombardi Cancer Clinic, Phone: 414-649-5717

West Allis Memorial Hospital, West Allis, Wisconsin 53227, United States; Recruiting
Clinical Trials Office - West Allis Memorial Hospital, Phone: 414-649-5717

Welch Cancer Center at Sheridan Memorial Hospital, Sheridan, Wyoming 82801, United States; Recruiting
Benjamin T. Marchello, MD, Phone: 307-674-6022

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: March 2006
Last updated: November 1, 2008