Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
23 octobre 2017 mis à jour par: Radiation Therapy Oncology Group
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
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.
Aperçu de l'étude
Statut
Complété
Les conditions
Description détaillée
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.
Type d'étude
Interventionnel
Inscription (Réel)
109
Phase
- Phase 3
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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British Columbia
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Victoria, British Columbia, Canada, V8R 6V5
- British Columbia Cancer Agency - Vancouver Island Centre
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Canada, A1B 3V6
- Doctor H. Bliss Murphy Cancer Centre
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Ontario
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Hamilton, Ontario, Canada, L8V 5C2
- Margaret and Charles Juravinski Cancer Centre
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Thunder Bay, Ontario, Canada, P7B 6V4
- Cancer Care Program at Thunder Bay Regional Health Sciences
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Quebec
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Montreal, Quebec, Canada, H1T 2M4
- Maisonneuve-Rosemont Hospital
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Quebec City, Quebec, Canada, G1R 2J6
- Centre Hospitalier Universitaire de Quebec
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Sherbrooke, Quebec, Canada, J1H 5N4
- CHUS-Hopital Fleurimont
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Saskatchewan
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Regina, Saskatchewan, Canada, S4T 7T1
- Allan Blair Cancer Centre at Pasqua Hospital
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California
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Chico, California, États-Unis, 95926
- Enloe Cancer Center at Enloe Medical Center
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Los Angeles, California, États-Unis, 90089-9181
- USC/Norris Comprehensive Cancer Center and Hospital
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Pomona, California, États-Unis, 91767
- Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
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Roseville, California, États-Unis, 95661
- Radiation Oncology Center - Roseville
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Sacramento, California, États-Unis, 95815
- Radiological Associates of Sacramento Medical Group, Incorporated
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Colorado
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Colorado Springs, Colorado, États-Unis, 80933
- Penrose Cancer Center at Penrose Hospital
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Pueblo, Colorado, États-Unis, 81004
- St. Mary - Corwin Regional Medical Center
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Georgia
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Gainesville, Georgia, États-Unis, 30501
- Northeast Georgia Medical Center
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Illinois
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Alton, Illinois, États-Unis, 62002
- Saint Anthony's Hospital at Saint Anthony's Health Center
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Arlington Heights, Illinois, États-Unis, 60005
- Northwest Community Hospital
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Harvey, Illinois, États-Unis, 60426
- Ingalls Cancer Care Center at Ingalls Memorial Hospital
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Olympia Fields, Illinois, États-Unis, 60461
- Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
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Urbana, Illinois, États-Unis, 61801
- CCOP - Carle Cancer Center
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Indiana
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Goshen, Indiana, États-Unis, 46526
- Center for Cancer Care at Goshen General Hospital
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Indianapolis, Indiana, États-Unis, 46202
- Methodist Cancer Center at Methodist Hospital
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Kentucky
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Lexington, Kentucky, États-Unis, 40536-0093
- Lucille P. Markey Cancer Center at University of Kentucky
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Maryland
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Baltimore, Maryland, États-Unis, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Baltimore, Maryland, États-Unis, 21229
- St. Agnes Hospital Cancer Center
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Michigan
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Detroit, Michigan, États-Unis, 48202
- Josephine Ford Cancer Center at Henry Ford Hospital
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Detroit, Michigan, États-Unis, 48201-1379
- Barbara Ann Karmanos Cancer Institute
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Kalamazoo, Michigan, États-Unis, 49007-3731
- West Michigan Cancer Center
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Minnesota
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Saint Cloud, Minnesota, États-Unis, 56303
- CentraCare Clinic - River Campus
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Saint Cloud, Minnesota, États-Unis, 56303
- Coborn Cancer Center
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Missouri
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Cape Girardeau, Missouri, États-Unis, 63701
- Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
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Kansas City, Missouri, États-Unis, 64131
- CCOP - Kansas City
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Saint Louis, Missouri, États-Unis, 63141
- CCOP - St. Louis-Cape Girardeau
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Saint Louis, Missouri, États-Unis, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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Saint Louis, Missouri, États-Unis, 63141
- David C. Pratt Cancer Center at St. John's Mercy
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Springfield, Missouri, États-Unis, 65804
- St. John's Regional Health Center
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Springfield, Missouri, États-Unis, 65807
- Hulston Cancer Center at Cox Medical Center South
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Montana
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Billings, Montana, États-Unis, 59101
- CCOP - Montana Cancer Consortium
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Billings, Montana, États-Unis, 59101
- Northern Rockies Radiation Oncology Center
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Great Falls, Montana, États-Unis, 59405
- Great Falls Clinic - Main Facility
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Nevada
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Las Vegas, Nevada, États-Unis, 89102
- University Medical Center of Southern Nevada
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Las Vegas, Nevada, États-Unis, 89106
- CCOP - Nevada Cancer Research Foundation
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Reno, Nevada, États-Unis, 89502
- Renown Institute for Cancer at Renown Regional Medical Center
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New Hampshire
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Keene, New Hampshire, États-Unis, 03431
- Kingsbury Center for Cancer Care at Cheshire Medical Center
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Lebanon, New Hampshire, États-Unis, 03756-0002
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
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New Jersey
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Camden, New Jersey, États-Unis, 08103
- Cancer Institute of New Jersey at Cooper University Hospital - Camden
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Vineland, New Jersey, États-Unis, 08360
- Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
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Voorhees, New Jersey, États-Unis, 08043
- Cancer Institute of New Jersey at Cooper - Voorhees
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New York
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Binghamton, New York, États-Unis, 13905
- Lourdes Regional Cancer Center
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Brooklyn, New York, États-Unis, 11209
- Veterans Affairs Medical Center - Brooklyn
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Buffalo, New York, États-Unis, 14263-0001
- Roswell Park Cancer Institute
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East Syracuse, New York, États-Unis, 13057
- CCOP - Hematology-Oncology Associates of Central New York
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North Carolina
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Asheville, North Carolina, États-Unis, 28801
- Mission Hospitals - Memorial Campus
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Goldsboro, North Carolina, États-Unis, 27534
- Wayne Radiation Oncology
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Raleigh, North Carolina, États-Unis, 27607
- Cancer Centers of North Carolina - Raleigh
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Wilson, North Carolina, États-Unis, 27893
- Wilmed Radiation Oncology Services
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Ohio
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Akron, Ohio, États-Unis, 44307
- McDowell Cancer Center at Akron General Medical Center
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Akron, Ohio, États-Unis, 44309-2090
- Summa Center for Cancer Care at Akron City Hospital
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Cincinnati, Ohio, États-Unis, 45267
- Charles M. Barrett Cancer Center at University Hospital
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Salem, Ohio, États-Unis, 44460
- Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
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West Chester, Ohio, États-Unis, 45069
- Precision Radiotherapy at University Pointe
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Wooster, Ohio, États-Unis, 44691
- Cancer Treatment Center
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Pennsylvania
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Abington, Pennsylvania, États-Unis, 19001
- Rosenfeld Cancer Center at Abington Memorial Hospital
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Bryn Mawr, Pennsylvania, États-Unis, 19010
- Bryn Mawr Hospital
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Gettysburg, Pennsylvania, États-Unis, 17325
- Adams Cancer Center
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Paoli, Pennsylvania, États-Unis, 19301-1792
- Cancer Center of Paoli Memorial Hospital
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Philadelphia, Pennsylvania, États-Unis, 19111-2497
- Fox Chase Cancer Center - Philadelphia
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Wynnewood, Pennsylvania, États-Unis, 19096
- Lankenau Cancer Center at Lankenau Hospital
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York, Pennsylvania, États-Unis, 17405
- York Cancer Center at Apple Hill Medical Center
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Tennessee
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Kingsport, Tennessee, États-Unis, 37662
- Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
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Utah
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Murray, Utah, États-Unis, 84157
- Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
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Ogden, Utah, États-Unis, 84403
- Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
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Provo, Utah, États-Unis, 84604
- Utah Valley Regional Medical Center - Provo
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Saint George, Utah, États-Unis, 84770
- Dixie Regional Medical Center - East Campus
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Salt Lake City, Utah, États-Unis, 84143
- LDS Hospital
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Vermont
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Saint Johnsbury, Vermont, États-Unis, 05819
- Norris Cotton Cancer Center - North
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Virginia
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Norfolk, Virginia, États-Unis, 23507
- Sentara Cancer Institute at Sentara Norfolk General Hospital
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Portsmouth, Virginia, États-Unis, 23708-2197
- Naval Medical Center - Portsmouth
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Washington
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Yakima, Washington, États-Unis, 98902
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
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Wisconsin
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Appleton, Wisconsin, États-Unis, 54911
- Theda Care Cancer Institute
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Green Bay, Wisconsin, États-Unis, 54307-3508
- St. Vincent Hospital Regional Cancer Center
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Marinette, Wisconsin, États-Unis, 54143
- Bay Area Cancer Care Center at Bay Area Medical Center
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Menomonee Falls, Wisconsin, États-Unis, 53051
- Community Memorial Hospital Cancer Care Center
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Milwaukee, Wisconsin, États-Unis, 53226
- Medical College of Wisconsin Cancer Center
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Milwaukee, Wisconsin, États-Unis, 53295
- Veterans Affairs Medical Center - Milwaukee
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Milwaukee, Wisconsin, États-Unis, 53215
- Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
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West Allis, Wisconsin, États-Unis, 53227
- West Allis Memorial Hospital
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Homme
La description
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
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Soins de soutien
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: 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.
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A single dose of 500 mg of elemental calcium orally each day for 3 years.
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.
Autres noms:
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 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.
400 IU (10μg), orally each day for 3 years.
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Comparateur actif: Control
Vitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
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A single dose of 500 mg of elemental calcium orally each day for 3 years.
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 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.
400 IU (10μg), orally each day for 3 years.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Freedom From Any Bone Fracture (FABF) Rate at Three Years
Délai: From randomization to 3 years
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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.
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From randomization to 3 years
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Percent Change in Bone Mineral Density at 3 Years
Délai: Baseline, 3 years from start of treatment
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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.
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Baseline, 3 years from start of treatment
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Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 Years
Délai: Baseline, 3 years from start of treatment
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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.
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Baseline, 3 years from start of treatment
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Utility of the Use of Bisphosphonates as Assessed by Quality-adjusted Survival
Délai: From pre-treatment to 3 years from start of treatment
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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.
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From pre-treatment to 3 years from start of treatment
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Colleen A. Lawton, MD, Medical College of Wisconsin
- Chaise d'étude: Matthew R. Smith, MD, Massachusetts General Hospital
- Chaise d'étude: Margaret Chamberlain-Wilmoth, PhD, MSS, RN, Carolinas Medical Center - University
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mars 2006
Achèvement primaire (Réel)
1 novembre 2014
Achèvement de l'étude (Réel)
1 novembre 2014
Dates d'inscription aux études
Première soumission
23 mai 2006
Première soumission répondant aux critères de contrôle qualité
23 mai 2006
Première publication (Estimation)
25 mai 2006
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
29 novembre 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
23 octobre 2017
Dernière vérification
1 octobre 2017
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies métaboliques
- Tumeurs
- Tumeurs urogénitales
- Tumeurs par site
- Tumeurs génitales, homme
- Maladies de la prostate
- Maladies musculo-squelettiques
- Maladies osseuses
- Maladies osseuses métaboliques
- Tumeurs prostatiques
- Ostéoporose
- Effets physiologiques des médicaments
- Micronutriments
- Vitamines
- Agents de conservation de la densité osseuse
- Hormones et agents régulateurs du calcium
- Vitamine D
- Calcium
- Acide zolédronique
Autres numéros d'identification d'étude
- RTOG 0518
- CDR0000476469
- NCI-2009-00884 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .