Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
23 de octubre de 2017 actualizado por: 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.
Descripción general del estudio
Estado
Terminado
Condiciones
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
109
Fase
- Fase 3
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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British Columbia
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Victoria, British Columbia, Canadá, 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, Canadá, A1B 3V6
- Doctor H. Bliss Murphy Cancer Centre
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Ontario
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Hamilton, Ontario, Canadá, L8V 5C2
- Margaret and Charles Juravinski Cancer Centre
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Thunder Bay, Ontario, Canadá, P7B 6V4
- Cancer Care Program at Thunder Bay Regional Health Sciences
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Quebec
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Montreal, Quebec, Canadá, H1T 2M4
- Maisonneuve-Rosemont Hospital
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Quebec City, Quebec, Canadá, G1R 2J6
- Centre Hospitalier Universitaire de Quebec
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Sherbrooke, Quebec, Canadá, J1H 5N4
- CHUS-Hopital Fleurimont
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Saskatchewan
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Regina, Saskatchewan, Canadá, S4T 7T1
- Allan Blair Cancer Centre at Pasqua Hospital
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California
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Chico, California, Estados Unidos, 95926
- Enloe Cancer Center at Enloe Medical Center
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Los Angeles, California, Estados Unidos, 90089-9181
- USC/Norris Comprehensive Cancer Center and Hospital
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Pomona, California, Estados Unidos, 91767
- Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
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Roseville, California, Estados Unidos, 95661
- Radiation Oncology Center - Roseville
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Sacramento, California, Estados Unidos, 95815
- Radiological Associates of Sacramento Medical Group, Incorporated
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Colorado
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Colorado Springs, Colorado, Estados Unidos, 80933
- Penrose Cancer Center at Penrose Hospital
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Pueblo, Colorado, Estados Unidos, 81004
- St. Mary - Corwin Regional Medical Center
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Georgia
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Gainesville, Georgia, Estados Unidos, 30501
- Northeast Georgia Medical Center
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Illinois
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Alton, Illinois, Estados Unidos, 62002
- Saint Anthony's Hospital at Saint Anthony's Health Center
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Arlington Heights, Illinois, Estados Unidos, 60005
- Northwest Community Hospital
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Harvey, Illinois, Estados Unidos, 60426
- Ingalls Cancer Care Center at Ingalls Memorial Hospital
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Olympia Fields, Illinois, Estados Unidos, 60461
- Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
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Urbana, Illinois, Estados Unidos, 61801
- CCOP - Carle Cancer Center
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Indiana
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Goshen, Indiana, Estados Unidos, 46526
- Center for Cancer Care at Goshen General Hospital
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Indianapolis, Indiana, Estados Unidos, 46202
- Methodist Cancer Center at Methodist Hospital
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Kentucky
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Lexington, Kentucky, Estados Unidos, 40536-0093
- Lucille P. Markey Cancer Center at University of Kentucky
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Maryland
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Baltimore, Maryland, Estados Unidos, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Baltimore, Maryland, Estados Unidos, 21229
- St. Agnes Hospital Cancer Center
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Michigan
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Detroit, Michigan, Estados Unidos, 48202
- Josephine Ford Cancer Center at Henry Ford Hospital
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Detroit, Michigan, Estados Unidos, 48201-1379
- Barbara Ann Karmanos Cancer Institute
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Kalamazoo, Michigan, Estados Unidos, 49007-3731
- West Michigan Cancer Center
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Minnesota
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Saint Cloud, Minnesota, Estados Unidos, 56303
- CentraCare Clinic - River Campus
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Saint Cloud, Minnesota, Estados Unidos, 56303
- Coborn Cancer Center
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Missouri
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Cape Girardeau, Missouri, Estados Unidos, 63701
- Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
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Kansas City, Missouri, Estados Unidos, 64131
- CCOP - Kansas City
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Saint Louis, Missouri, Estados Unidos, 63141
- CCOP - St. Louis-Cape Girardeau
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Saint Louis, Missouri, Estados Unidos, 63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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Saint Louis, Missouri, Estados Unidos, 63141
- David C. Pratt Cancer Center at St. John's Mercy
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Springfield, Missouri, Estados Unidos, 65804
- St. John's Regional Health Center
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Springfield, Missouri, Estados Unidos, 65807
- Hulston Cancer Center at Cox Medical Center South
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Montana
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Billings, Montana, Estados Unidos, 59101
- CCOP - Montana Cancer Consortium
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Billings, Montana, Estados Unidos, 59101
- Northern Rockies Radiation Oncology Center
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Great Falls, Montana, Estados Unidos, 59405
- Great Falls Clinic - Main Facility
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Nevada
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Las Vegas, Nevada, Estados Unidos, 89102
- University Medical Center of Southern Nevada
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Las Vegas, Nevada, Estados Unidos, 89106
- CCOP - Nevada Cancer Research Foundation
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Reno, Nevada, Estados Unidos, 89502
- Renown Institute for Cancer at Renown Regional Medical Center
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New Hampshire
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Keene, New Hampshire, Estados Unidos, 03431
- Kingsbury Center for Cancer Care at Cheshire Medical Center
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Lebanon, New Hampshire, Estados Unidos, 03756-0002
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
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New Jersey
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Camden, New Jersey, Estados Unidos, 08103
- Cancer Institute of New Jersey at Cooper University Hospital - Camden
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Vineland, New Jersey, Estados Unidos, 08360
- Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
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Voorhees, New Jersey, Estados Unidos, 08043
- Cancer Institute of New Jersey at Cooper - Voorhees
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New York
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Binghamton, New York, Estados Unidos, 13905
- Lourdes Regional Cancer Center
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Brooklyn, New York, Estados Unidos, 11209
- Veterans Affairs Medical Center - Brooklyn
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Buffalo, New York, Estados Unidos, 14263-0001
- Roswell Park Cancer Institute
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East Syracuse, New York, Estados Unidos, 13057
- CCOP - Hematology-Oncology Associates of Central New York
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North Carolina
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Asheville, North Carolina, Estados Unidos, 28801
- Mission Hospitals - Memorial Campus
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Goldsboro, North Carolina, Estados Unidos, 27534
- Wayne Radiation Oncology
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Raleigh, North Carolina, Estados Unidos, 27607
- Cancer Centers of North Carolina - Raleigh
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Wilson, North Carolina, Estados Unidos, 27893
- Wilmed Radiation Oncology Services
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Ohio
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Akron, Ohio, Estados Unidos, 44307
- McDowell Cancer Center at Akron General Medical Center
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Akron, Ohio, Estados Unidos, 44309-2090
- Summa Center for Cancer Care at Akron City Hospital
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Cincinnati, Ohio, Estados Unidos, 45267
- Charles M. Barrett Cancer Center at University Hospital
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Salem, Ohio, Estados Unidos, 44460
- Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
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West Chester, Ohio, Estados Unidos, 45069
- Precision Radiotherapy at University Pointe
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Wooster, Ohio, Estados Unidos, 44691
- Cancer Treatment Center
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Pennsylvania
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Abington, Pennsylvania, Estados Unidos, 19001
- Rosenfeld Cancer Center at Abington Memorial Hospital
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Bryn Mawr, Pennsylvania, Estados Unidos, 19010
- Bryn Mawr Hospital
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Gettysburg, Pennsylvania, Estados Unidos, 17325
- Adams Cancer Center
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Paoli, Pennsylvania, Estados Unidos, 19301-1792
- Cancer Center of Paoli Memorial Hospital
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Philadelphia, Pennsylvania, Estados Unidos, 19111-2497
- Fox Chase Cancer Center - Philadelphia
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Wynnewood, Pennsylvania, Estados Unidos, 19096
- Lankenau Cancer Center at Lankenau Hospital
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York, Pennsylvania, Estados Unidos, 17405
- York Cancer Center at Apple Hill Medical Center
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Tennessee
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Kingsport, Tennessee, Estados Unidos, 37662
- Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
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Utah
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Murray, Utah, Estados Unidos, 84157
- Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
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Ogden, Utah, Estados Unidos, 84403
- Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
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Provo, Utah, Estados Unidos, 84604
- Utah Valley Regional Medical Center - Provo
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Saint George, Utah, Estados Unidos, 84770
- Dixie Regional Medical Center - East Campus
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Salt Lake City, Utah, Estados Unidos, 84143
- LDS Hospital
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Vermont
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Saint Johnsbury, Vermont, Estados Unidos, 05819
- Norris Cotton Cancer Center - North
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Virginia
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Norfolk, Virginia, Estados Unidos, 23507
- Sentara Cancer Institute at Sentara Norfolk General Hospital
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Portsmouth, Virginia, Estados Unidos, 23708-2197
- Naval Medical Center - Portsmouth
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Washington
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Yakima, Washington, Estados Unidos, 98902
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
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Wisconsin
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Appleton, Wisconsin, Estados Unidos, 54911
- Theda Care Cancer Institute
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Green Bay, Wisconsin, Estados Unidos, 54307-3508
- St. Vincent Hospital Regional Cancer Center
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Marinette, Wisconsin, Estados Unidos, 54143
- Bay Area Cancer Care Center at Bay Area Medical Center
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Menomonee Falls, Wisconsin, Estados Unidos, 53051
- Community Memorial Hospital Cancer Care Center
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin Cancer Center
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Milwaukee, Wisconsin, Estados Unidos, 53295
- Veterans Affairs Medical Center - Milwaukee
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Milwaukee, Wisconsin, Estados Unidos, 53215
- Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
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West Allis, Wisconsin, Estados Unidos, 53227
- West Allis Memorial Hospital
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Masculino
Descripción
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 de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Cuidados de apoyo
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: 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.
Otros nombres:
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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Comparador activo: 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Freedom From Any Bone Fracture (FABF) Rate at Three Years
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percent Change in Bone Mineral Density at 3 Years
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Colleen A. Lawton, MD, Medical College of Wisconsin
- Silla de estudio: Matthew R. Smith, MD, Massachusetts General Hospital
- Silla de estudio: Margaret Chamberlain-Wilmoth, PhD, MSS, RN, Carolinas Medical Center - University
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de marzo de 2006
Finalización primaria (Actual)
1 de noviembre de 2014
Finalización del estudio (Actual)
1 de noviembre de 2014
Fechas de registro del estudio
Enviado por primera vez
23 de mayo de 2006
Primero enviado que cumplió con los criterios de control de calidad
23 de mayo de 2006
Publicado por primera vez (Estimar)
25 de mayo de 2006
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
29 de noviembre de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
23 de octubre de 2017
Última verificación
1 de octubre de 2017
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades metabólicas
- Neoplasias
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias Genitales Masculinas
- Enfermedades prostáticas
- Enfermedades musculoesqueléticas
- Enfermedades óseas
- Enfermedades Óseas Metabólicas
- Neoplasias prostáticas
- Osteoporosis
- Efectos fisiológicos de las drogas
- Micronutrientes
- Vitaminas
- Agentes de conservación de la densidad ósea
- Hormonas y agentes reguladores del calcio
- Vitamina D
- Calcio
- Ácido zoledrónico
Otros números de identificación del estudio
- RTOG 0518
- CDR0000476469
- NCI-2009-00884 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .