Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
23 de outubro de 2017 atualizado 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.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
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 estudo
Intervencional
Inscrição (Real)
109
Estágio
- Fase 3
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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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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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Macho
Descrição
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
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Cuidados de suporte
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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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.
Outros nomes:
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.
|
|
Comparador Ativo: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Freedom From Any Bone Fracture (FABF) Rate at Three Years
Prazo: 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.
|
From randomization to 3 years
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Percent Change in Bone Mineral Density at 3 Years
Prazo: 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
Prazo: Baseline, 3 years from start of treatment
|
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
Prazo: From pre-treatment to 3 years from start of treatment
|
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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Colleen A. Lawton, MD, Medical College of Wisconsin
- Cadeira de estudo: Matthew R. Smith, MD, Massachusetts General Hospital
- Cadeira de estudo: Margaret Chamberlain-Wilmoth, PhD, MSS, RN, Carolinas Medical Center - University
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de março de 2006
Conclusão Primária (Real)
1 de novembro de 2014
Conclusão do estudo (Real)
1 de novembro de 2014
Datas de inscrição no estudo
Enviado pela primeira vez
23 de maio de 2006
Enviado pela primeira vez que atendeu aos critérios de CQ
23 de maio de 2006
Primeira postagem (Estimativa)
25 de maio de 2006
Atualizações de registro de estudo
Última Atualização Postada (Real)
29 de novembro de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
23 de outubro de 2017
Última verificação
1 de outubro de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças Metabólicas
- Neoplasias
- Neoplasias urogenitais
- Neoplasias por local
- Neoplasias Genitais Masculinas
- Doenças prostáticas
- Doenças musculoesqueléticas
- Doenças ósseas
- Doenças Ósseas Metabólicas
- Neoplasias prostáticas
- Osteoporose
- Efeitos Fisiológicos das Drogas
- Micronutrientes
- Vitaminas
- Agentes de Conservação da Densidade Óssea
- Hormônios e Agentes Reguladores de Cálcio
- Vitamina D
- Cálcio
- Ácido Zoledrônico
Outros números de identificação do estudo
- RTOG 0518
- CDR0000476469
- NCI-2009-00884 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .