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

NCT ID: NCT00329797

Last Updated: 2017-11-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

109 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2014-11-30

Brief Summary

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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

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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.

Conditions

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Osteoporosis Prostate Cancer

Keywords

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osteoporosis adenocarcinoma of the prostate stage IIB prostate cancer stage IIA prostate cancer stage III prostate cancer stage IV prostate cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Zoledronic Acid

Zoledronic acid q 6 months plus Vitamin D and calcium supplement for 3 years in addition to concurrent radiation therapy and LHRH therapy.

Group Type EXPERIMENTAL

Calcium

Intervention Type DIETARY_SUPPLEMENT

A single dose of 500 mg of elemental calcium orally each day for 3 years.

Zoledronic acid

Intervention Type DIETARY_SUPPLEMENT

Patients receive IV over 15 minutes once every 6 months for 3 years. The goal dose of zoledronic acid is 4 mg, but the selection of dose is determined based on calculated creatinine clearance at baseline.

radiation therapy

Intervention Type RADIATION

Patients must receive external beam irradiation, brachytherapy (HDR or LDR), or a combination of external beam irradiation and brachytherapy at the discretion of the treating physician. Dose/duration also will be at the discretion of the treating physician; however, dose will not exceed 45 Gy to 100% of the proximal femur, and no proximal femur will receive ≥ 60 Gy.

LHRH

Intervention Type DRUG

LHRH therapy must take place for a minimum of one year. Choice of LHRH agonist, dose, and duration are at the discretion of the treating physician.

Vitamin D

Intervention Type DIETARY_SUPPLEMENT

400 IU (10μg), orally each day for 3 years.

Control

Vitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.

Group Type ACTIVE_COMPARATOR

Calcium

Intervention Type DIETARY_SUPPLEMENT

A single dose of 500 mg of elemental calcium orally each day for 3 years.

radiation therapy

Intervention Type RADIATION

Patients must receive external beam irradiation, brachytherapy (HDR or LDR), or a combination of external beam irradiation and brachytherapy at the discretion of the treating physician. Dose/duration also will be at the discretion of the treating physician; however, dose will not exceed 45 Gy to 100% of the proximal femur, and no proximal femur will receive ≥ 60 Gy.

LHRH

Intervention Type DRUG

LHRH therapy must take place for a minimum of one year. Choice of LHRH agonist, dose, and duration are at the discretion of the treating physician.

Vitamin D

Intervention Type DIETARY_SUPPLEMENT

400 IU (10μg), orally each day for 3 years.

Interventions

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Calcium

A single dose of 500 mg of elemental calcium orally each day for 3 years.

Intervention Type DIETARY_SUPPLEMENT

Zoledronic acid

Patients receive IV over 15 minutes once every 6 months for 3 years. The goal dose of zoledronic acid is 4 mg, but the selection of dose is determined based on calculated creatinine clearance at baseline.

Intervention Type DIETARY_SUPPLEMENT

radiation therapy

Patients must receive external beam irradiation, brachytherapy (HDR or LDR), or a combination of external beam irradiation and brachytherapy at the discretion of the treating physician. Dose/duration also will be at the discretion of the treating physician; however, dose will not exceed 45 Gy to 100% of the proximal femur, and no proximal femur will receive ≥ 60 Gy.

Intervention Type RADIATION

LHRH

LHRH therapy must take place for a minimum of one year. Choice of LHRH agonist, dose, and duration are at the discretion of the treating physician.

Intervention Type DRUG

Vitamin D

400 IU (10μg), orally each day for 3 years.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Zometa zoledronate

Eligibility Criteria

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Inclusion Criteria

* Zubrod Performance Status 0-1 within 16 weeks prior to registration; (8/16/07)
* Age ≥ 18;
* Serum creatinine within 4 weeks prior to registration (8/16/07)
* Corrected serum calcium ≥ 8.4 and ≤ 10.6 mg/dl within 8 weeks prior to registration; note: for patients with an albumin of 4.0, corrected calcium=measured calcium. The formula for corrected calcium if serum albumin value is above or below 4.0 is as follows: Corrected calcium (mg/dl) = (4 - \[patient's albumin (g/dl)\] x 0.8) + patient's measured calcium (mg/dl)
* Patients who are sexually active must be willing/able to use medically acceptable forms of contraception, as the treatment involved in this study may be significantly teratogenic.
* Patient agrees to refrain from using all products listed in Section 9.2, "Non-permitted Supportive Therapy";
* Post-prostatectomy patients are eligible.
* Patient must sign study specific informed consent prior to study entry.

Ineligibility criteria:

* Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; e.g., carcinoma in situ of the breast or oral cavity are permissible;
* Patients with baseline T scores of ≤ -2.5 are excluded.
* Patients with baseline calculated creatinine clearance \< 30 mL/min (estimated by Cockcroft-Gault formula below) are excluded. creatinine clearance male = \[(140 - age) x (wt in kg)\] / \[(serum creatinine) x (72)\]
* Prior bisphosphonate therapy;
* Prior pelvic radiation (other than for current prostate cancer) or prior systemic radiotherapeutic agents, such as strontium or samarium;
* Patients receiving systemic chemotherapy, steroids, growth hormones, or calcitonin;
* Patients with a history of Paget's disease or with uncontrolled thyroid or parathyroid dysfunction or with other diseases that influence bone metabolism;
* Known hypersensitivity to zoledronic acid or other bisphosphonates;
* Active dental problems at study entry, including infection of the teeth or jawbone; dental or fixture trauma; or a current or prior diagnosis of osteonecrosis of the jaw, exposed bone in the mouth, or slow healing after dental procedures;
* Recent or planned
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Radiation Therapy Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Colleen A. Lawton, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Matthew R. Smith, MD

Role: STUDY_CHAIR

Massachusetts General Hospital

Margaret Chamberlain-Wilmoth, PhD, MSS, RN

Role: STUDY_CHAIR

Carolinas Medical Center - University

Locations

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Enloe Cancer Center at Enloe Medical Center

Chico, California, United States

Site Status

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

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

Pomona, California, United States

Site Status

Radiation Oncology Center - Roseville

Roseville, California, United States

Site Status

Radiological Associates of Sacramento Medical Group, Incorporated

Sacramento, California, United States

Site Status

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, United States

Site Status

St. Mary - Corwin Regional Medical Center

Pueblo, Colorado, United States

Site Status

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Site Status

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

Alton, Illinois, United States

Site Status

Northwest Community Hospital

Arlington Heights, Illinois, United States

Site Status

Ingalls Cancer Care Center at Ingalls Memorial Hospital

Harvey, Illinois, United States

Site Status

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

Olympia Fields, Illinois, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

Center for Cancer Care at Goshen General Hospital

Goshen, Indiana, United States

Site Status

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States

Site Status

St. Agnes Hospital Cancer Center

Baltimore, Maryland, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

CentraCare Clinic - River Campus

Saint Cloud, Minnesota, United States

Site Status

Coborn Cancer Center

Saint Cloud, Minnesota, United States

Site Status

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital

Cape Girardeau, Missouri, United States

Site Status

CCOP - Kansas City

Kansas City, Missouri, United States

Site Status

St. John's Regional Health Center

Springfield, Missouri, United States

Site Status

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, United States

Site Status

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

St Louis, Missouri, United States

Site Status

CCOP - Montana Cancer Consortium

Billings, Montana, United States

Site Status

Northern Rockies Radiation Oncology Center

Billings, Montana, United States

Site Status

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Site Status

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Site Status

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Renown Institute for Cancer at Renown Regional Medical Center

Reno, Nevada, United States

Site Status

Kingsbury Center for Cancer Care at Cheshire Medical Center

Keene, New Hampshire, United States

Site Status

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Cancer Institute of New Jersey at Cooper University Hospital - Camden

Camden, New Jersey, United States

Site Status

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, United States

Site Status

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Site Status

Lourdes Regional Cancer Center

Binghamton, New York, United States

Site Status

Veterans Affairs Medical Center - Brooklyn

Brooklyn, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - Hematology-Oncology Associates of Central New York

East Syracuse, New York, United States

Site Status

Mission Hospitals - Memorial Campus

Asheville, North Carolina, United States

Site Status

Wayne Radiation Oncology

Goldsboro, North Carolina, United States

Site Status

Cancer Centers of North Carolina - Raleigh

Raleigh, North Carolina, United States

Site Status

Wilmed Radiation Oncology Services

Wilson, North Carolina, United States

Site Status

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, United States

Site Status

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States

Site Status

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Site Status

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

Salem, Ohio, United States

Site Status

Precision Radiotherapy at University Pointe

West Chester, Ohio, United States

Site Status

Cancer Treatment Center

Wooster, Ohio, United States

Site Status

Rosenfeld Cancer Center at Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, United States

Site Status

Adams Cancer Center

Gettysburg, Pennsylvania, United States

Site Status

Cancer Center of Paoli Memorial Hospital

Paoli, Pennsylvania, United States

Site Status

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, United States

Site Status

York Cancer Center at Apple Hill Medical Center

York, Pennsylvania, United States

Site Status

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center

Kingsport, Tennessee, United States

Site Status

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Site Status

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

Ogden, Utah, United States

Site Status

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States

Site Status

LDS Hospital

Salt Lake City, Utah, United States

Site Status

Dixie Regional Medical Center - East Campus

St. George, Utah, United States

Site Status

Norris Cotton Cancer Center - North

Saint Johnsbury, Vermont, United States

Site Status

Sentara Cancer Institute at Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Site Status

Naval Medical Center - Portsmouth

Portsmouth, Virginia, United States

Site Status

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, United States

Site Status

Theda Care Cancer Institute

Appleton, Wisconsin, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, United States

Site Status

Community Memorial Hospital Cancer Care Center

Menomonee Falls, Wisconsin, United States

Site Status

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

Milwaukee, Wisconsin, United States

Site Status

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, United States

Site Status

West Allis Memorial Hospital

West Allis, Wisconsin, United States

Site Status

British Columbia Cancer Agency - Vancouver Island Centre

Victoria, British Columbia, Canada

Site Status

Doctor H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

Site Status

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

Cancer Care Program at Thunder Bay Regional Health Sciences

Thunder Bay, Ontario, Canada

Site Status

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

Site Status

CHUS-Hopital Fleurimont

Sherbrooke, Quebec, Canada

Site Status

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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CDR0000476469

Identifier Type: -

Identifier Source: secondary_id

NCI-2009-00884

Identifier Type: REGISTRY

Identifier Source: secondary_id

RTOG 0518

Identifier Type: -

Identifier Source: org_study_id