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

NCT00329797 | Completed Phase 3 Results DMC

• 3 other identifiers: RTOG 0518CDR0000476469NCI-2009-00884
• Study Type: interventional
• Target: 109
• Locations: 2 countries
• Sites: 88

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.

Conditions

Osteoporosis; Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Freedom From Any Bone Fracture (FABF) Rate at Three 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.

  From randomization to 3 years

Secondary Outcomes (3)

• Percent Change in Bone Mineral Density at 3 Years

  Baseline, 3 years from start of treatment

• Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 Years

  Baseline, 3 years from start of treatment

• Utility of the Use of Bisphosphonates as Assessed by Quality-adjusted Survival

  From pre-treatment to 3 years from start of treatment

Study Arms (2)

Zoledronic Acid

EXPERIMENTAL

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

Dietary Supplement: Calcium; Dietary Supplement: Zoledronic acid; Radiation: radiation therapy; Drug: LHRH; Dietary Supplement: Vitamin D

Control

ACTIVE COMPARATOR

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

Dietary Supplement: Calcium; Radiation: radiation therapy; Drug: LHRH; Dietary Supplement: Vitamin D

Interventions

Calcium DIETARY_SUPPLEMENT

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

Control; Zoledronic Acid

Zoledronic acid 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.

Also known as: Zometa, zoledronate

Zoledronic Acid

radiation therapy 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.

Control; Zoledronic Acid

LHRH 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.

Control; Zoledronic Acid

Vitamin D DIETARY_SUPPLEMENT

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

Control; Zoledronic Acid

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Eligibility criteria: * Pathologically (histologically or cytologically) proven diagnosis of adenocarcinoma of the prostate within 12 months of registration; * Any one of the following clinical stages: * T3 disease, any N stage, M0 with any Gleason score and any prostate-specific antigen (PSA); \< T3 stage, any N stage, M0 with Gleason's score ≥ 8 and any PSA; \< T3 stage, any N stage, M0 with Gleason's score 7 and PSA ≥ 15 nanograms/ml; \< T3 stage, any N stage, M0 with Gleason score \< 7 and PSA ≥ 20 nanograms/ml. * A negative bone scan for metastatic disease; * It is mandatory that the treating physician determine the planned duration of LHRH therapy prior to the site registering the patient (minimum 1 year of therapy); If patient is receiving pre-treatment LHRH therapy, it must have begun ≤ 6 months prior to registration. If pelvic radiation therapy (RT) has started, it must have begun ≤ 8 weeks prior to registration; * Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup to be done within 16 weeks prior to registration: * History/physical examination; * Dental evaluation, including history of dental surgery (e.g., extraction or implant); * Bone scan; * T and L spine films; * DXA scan: To be eligible the patient must have a scan on Lunar, Hologic, or Norland equipment only and the T scores in both the L spine and total hip must be \> negative 2.5; * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (88)

Enloe Cancer Center at Enloe Medical Center

Chico, California, 95926, United States

Location

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, 90089-9181, United States

Location

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

Pomona, California, 91767, United States

Location

Radiation Oncology Center - Roseville

Roseville, California, 95661, United States

Location

Radiological Associates of Sacramento Medical Group, Incorporated

Sacramento, California, 95815, United States

Location

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, 80933, United States

Location

St. Mary - Corwin Regional Medical Center

Pueblo, Colorado, 81004, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

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

Alton, Illinois, 62002, United States

Location

Northwest Community Hospital

Arlington Heights, Illinois, 60005, United States

Location

Ingalls Cancer Care Center at Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

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

Olympia Fields, Illinois, 60461, United States

Location

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Center for Cancer Care at Goshen General Hospital

Goshen, Indiana, 46526, United States

Location

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

St. Agnes Hospital Cancer Center

Baltimore, Maryland, 21229, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

CentraCare Clinic - River Campus

Saint Cloud, Minnesota, 56303, United States

Location

Coborn Cancer Center

Saint Cloud, Minnesota, 56303, United States

Location

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital

Cape Girardeau, Missouri, 63701, United States

Location

CCOP - Kansas City

Kansas City, Missouri, 64131, United States

Location

St. John's Regional Health Center

Springfield, Missouri, 65804, United States

Location

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, 65807, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, 63141, United States

Location

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

St Louis, Missouri, 63141, United States

Location

CCOP - Montana Cancer Consortium

Billings, Montana, 59101, United States

Location

Northern Rockies Radiation Oncology Center

Billings, Montana, 59101, United States

Location

Great Falls Clinic - Main Facility

Great Falls, Montana, 59405, United States

Location

University Medical Center of Southern Nevada

Las Vegas, Nevada, 89102, United States

Location

CCOP - Nevada Cancer Research Foundation

Las Vegas, Nevada, 89106, United States

Location

Renown Institute for Cancer at Renown Regional Medical Center

Reno, Nevada, 89502, United States

Location

Kingsbury Center for Cancer Care at Cheshire Medical Center

Keene, New Hampshire, 03431, United States

Location

Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0002, United States

Location

Cancer Institute of New Jersey at Cooper University Hospital - Camden

Camden, New Jersey, 08103, United States

Location

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, 08360, United States

Location

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, 08043, United States

Location

Lourdes Regional Cancer Center

Binghamton, New York, 13905, United States

Location

Veterans Affairs Medical Center - Brooklyn

Brooklyn, New York, 11209, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

CCOP - Hematology-Oncology Associates of Central New York

East Syracuse, New York, 13057, United States

Location

Mission Hospitals - Memorial Campus

Asheville, North Carolina, 28801, United States

Location

Wayne Radiation Oncology

Goldsboro, North Carolina, 27534, United States

Location

Cancer Centers of North Carolina - Raleigh

Raleigh, North Carolina, 27607, United States

Location

Wilmed Radiation Oncology Services

Wilson, North Carolina, 27893, United States

Location

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, 44307, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, 45267, United States

Location

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

Salem, Ohio, 44460, United States

Location

Precision Radiotherapy at University Pointe

West Chester, Ohio, 45069, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Rosenfeld Cancer Center at Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Adams Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

Cancer Center of Paoli Memorial Hospital

Paoli, Pennsylvania, 19301-1792, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, 19096, United States

Location

York Cancer Center at Apple Hill Medical Center

York, Pennsylvania, 17405, United States

Location

Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center

Kingsport, Tennessee, 37662, United States

Location

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, 84157, United States

Location

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

Ogden, Utah, 84403, United States

Location

Utah Valley Regional Medical Center - Provo

Provo, Utah, 84604, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

Dixie Regional Medical Center - East Campus

St. George, Utah, 84770, United States

Location

Norris Cotton Cancer Center - North

Saint Johnsbury, Vermont, 05819, United States

Location

Sentara Cancer Institute at Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Naval Medical Center - Portsmouth

Portsmouth, Virginia, 23708-2197, United States

Location

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital

Yakima, Washington, 98902, United States

Location

Theda Care Cancer Institute

Appleton, Wisconsin, 54911, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Bay Area Cancer Care Center at Bay Area Medical Center

Marinette, Wisconsin, 54143, United States

Location

Community Memorial Hospital Cancer Care Center

Menomonee Falls, Wisconsin, 53051, United States

Location

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

Milwaukee, Wisconsin, 53215, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, 53295, United States

Location

West Allis Memorial Hospital

West Allis, Wisconsin, 53227, United States

Location

British Columbia Cancer Agency - Vancouver Island Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

Doctor H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Care Program at Thunder Bay Regional Health Sciences

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

CHUS-Hopital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, S4T 7T1, Canada

Location

MeSH Terms

Conditions

Osteoporosis; Prostatic Neoplasms

Interventions

Calcium; Zoledronic Acid; Radiotherapy; Gonadotropin-Releasing Hormone; Vitamin D

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

This study stopped accrual early due to unmet targeted accrual goals with 109 subjects accrued out of 1272 planned, less than 10% than what was planned.

Results Point of Contact

• Title: Wendy Seiferheld, M.S.
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Colleen A. Lawton, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Matthew R. Smith, MD

  Massachusetts General Hospital

  STUDY CHAIR

• Margaret Chamberlain-Wilmoth, PhD, MSS, RN

  Carolinas Medical Center - University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2006
• First Posted: May 25, 2006
• Study Start: March 1, 2006
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: November 29, 2017
• Results First Posted: November 29, 2017

Record last verified: 2017-10

Locations

US (80); CA (8)