Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
2017年10月23日 更新者：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.
研究概览
地位
完全的
详细说明
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.
研究类型
介入性
注册 (实际的)
109
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
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British Columbia
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Victoria、British Columbia、加拿大、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、加拿大、A1B 3V6
- Doctor H. Bliss Murphy Cancer Centre
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Ontario
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Hamilton、Ontario、加拿大、L8V 5C2
- Margaret and Charles Juravinski Cancer Centre
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Thunder Bay、Ontario、加拿大、P7B 6V4
- Cancer Care Program at Thunder Bay Regional Health Sciences
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Quebec
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Montreal、Quebec、加拿大、H1T 2M4
- Maisonneuve-Rosemont Hospital
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Quebec City、Quebec、加拿大、G1R 2J6
- Centre Hospitalier Universitaire de Quebec
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Sherbrooke、Quebec、加拿大、J1H 5N4
- CHUS-Hopital Fleurimont
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Saskatchewan
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Regina、Saskatchewan、加拿大、S4T 7T1
- Allan Blair Cancer Centre at Pasqua Hospital
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-
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California
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Chico、California、美国、95926
- Enloe Cancer Center at Enloe Medical Center
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Los Angeles、California、美国、90089-9181
- USC/Norris Comprehensive Cancer Center and Hospital
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Pomona、California、美国、91767
- Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
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Roseville、California、美国、95661
- Radiation Oncology Center - Roseville
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Sacramento、California、美国、95815
- Radiological Associates of Sacramento Medical Group, Incorporated
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Colorado
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Colorado Springs、Colorado、美国、80933
- Penrose Cancer Center at Penrose Hospital
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Pueblo、Colorado、美国、81004
- St. Mary - Corwin Regional Medical Center
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Georgia
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Gainesville、Georgia、美国、30501
- Northeast Georgia Medical Center
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Illinois
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Alton、Illinois、美国、62002
- Saint Anthony's Hospital at Saint Anthony's Health Center
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Arlington Heights、Illinois、美国、60005
- Northwest Community Hospital
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Harvey、Illinois、美国、60426
- Ingalls Cancer Care Center at Ingalls Memorial Hospital
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Olympia Fields、Illinois、美国、60461
- Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
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Urbana、Illinois、美国、61801
- CCOP - Carle Cancer Center
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Indiana
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Goshen、Indiana、美国、46526
- Center for Cancer Care at Goshen General Hospital
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Indianapolis、Indiana、美国、46202
- Methodist Cancer Center at Methodist Hospital
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Kentucky
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Lexington、Kentucky、美国、40536-0093
- Lucille P. Markey Cancer Center at University of Kentucky
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Maryland
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Baltimore、Maryland、美国、21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Baltimore、Maryland、美国、21229
- St. Agnes Hospital Cancer Center
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Michigan
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Detroit、Michigan、美国、48202
- Josephine Ford Cancer Center at Henry Ford Hospital
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Detroit、Michigan、美国、48201-1379
- Barbara Ann Karmanos Cancer Institute
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Kalamazoo、Michigan、美国、49007-3731
- West Michigan Cancer Center
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Minnesota
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Saint Cloud、Minnesota、美国、56303
- CentraCare Clinic - River Campus
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Saint Cloud、Minnesota、美国、56303
- Coborn Cancer Center
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Missouri
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Cape Girardeau、Missouri、美国、63701
- Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
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Kansas City、Missouri、美国、64131
- CCOP - Kansas City
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Saint Louis、Missouri、美国、63141
- CCOP - St. Louis-Cape Girardeau
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Saint Louis、Missouri、美国、63110
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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Saint Louis、Missouri、美国、63141
- David C. Pratt Cancer Center at St. John's Mercy
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Springfield、Missouri、美国、65804
- St. John's Regional Health Center
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Springfield、Missouri、美国、65807
- Hulston Cancer Center at Cox Medical Center South
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Montana
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Billings、Montana、美国、59101
- CCOP - Montana Cancer Consortium
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Billings、Montana、美国、59101
- Northern Rockies Radiation Oncology Center
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Great Falls、Montana、美国、59405
- Great Falls Clinic - Main Facility
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Nevada
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Las Vegas、Nevada、美国、89102
- University Medical Center of Southern Nevada
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Las Vegas、Nevada、美国、89106
- CCOP - Nevada Cancer Research Foundation
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Reno、Nevada、美国、89502
- Renown Institute for Cancer at Renown Regional Medical Center
-
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New Hampshire
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Keene、New Hampshire、美国、03431
- Kingsbury Center for Cancer Care at Cheshire Medical Center
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Lebanon、New Hampshire、美国、03756-0002
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
-
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New Jersey
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Camden、New Jersey、美国、08103
- Cancer Institute of New Jersey at Cooper University Hospital - Camden
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Vineland、New Jersey、美国、08360
- Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
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Voorhees、New Jersey、美国、08043
- Cancer Institute of New Jersey at Cooper - Voorhees
-
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New York
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Binghamton、New York、美国、13905
- Lourdes Regional Cancer Center
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Brooklyn、New York、美国、11209
- Veterans Affairs Medical Center - Brooklyn
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Buffalo、New York、美国、14263-0001
- Roswell Park Cancer Institute
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East Syracuse、New York、美国、13057
- CCOP - Hematology-Oncology Associates of Central New York
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North Carolina
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Asheville、North Carolina、美国、28801
- Mission Hospitals - Memorial Campus
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Goldsboro、North Carolina、美国、27534
- Wayne Radiation Oncology
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Raleigh、North Carolina、美国、27607
- Cancer Centers of North Carolina - Raleigh
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Wilson、North Carolina、美国、27893
- Wilmed Radiation Oncology Services
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Ohio
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Akron、Ohio、美国、44307
- McDowell Cancer Center at Akron General Medical Center
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Akron、Ohio、美国、44309-2090
- Summa Center for Cancer Care at Akron City Hospital
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Cincinnati、Ohio、美国、45267
- Charles M. Barrett Cancer Center at University Hospital
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Salem、Ohio、美国、44460
- Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
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West Chester、Ohio、美国、45069
- Precision Radiotherapy at University Pointe
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Wooster、Ohio、美国、44691
- Cancer Treatment Center
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Pennsylvania
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Abington、Pennsylvania、美国、19001
- Rosenfeld Cancer Center at Abington Memorial Hospital
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Bryn Mawr、Pennsylvania、美国、19010
- Bryn Mawr Hospital
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Gettysburg、Pennsylvania、美国、17325
- Adams Cancer Center
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Paoli、Pennsylvania、美国、19301-1792
- Cancer Center of Paoli Memorial Hospital
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Philadelphia、Pennsylvania、美国、19111-2497
- Fox Chase Cancer Center - Philadelphia
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Wynnewood、Pennsylvania、美国、19096
- Lankenau Cancer Center at Lankenau Hospital
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York、Pennsylvania、美国、17405
- York Cancer Center at Apple Hill Medical Center
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Tennessee
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Kingsport、Tennessee、美国、37662
- Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
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Utah
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Murray、Utah、美国、84157
- Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
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Ogden、Utah、美国、84403
- Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
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Provo、Utah、美国、84604
- Utah Valley Regional Medical Center - Provo
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Saint George、Utah、美国、84770
- Dixie Regional Medical Center - East Campus
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Salt Lake City、Utah、美国、84143
- LDS Hospital
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Vermont
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Saint Johnsbury、Vermont、美国、05819
- Norris Cotton Cancer Center - North
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Virginia
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Norfolk、Virginia、美国、23507
- Sentara Cancer Institute at Sentara Norfolk General Hospital
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Portsmouth、Virginia、美国、23708-2197
- Naval Medical Center - Portsmouth
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Washington
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Yakima、Washington、美国、98902
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
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Wisconsin
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Appleton、Wisconsin、美国、54911
- Theda Care Cancer Institute
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Green Bay、Wisconsin、美国、54307-3508
- St. Vincent Hospital Regional Cancer Center
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Marinette、Wisconsin、美国、54143
- Bay Area Cancer Care Center at Bay Area Medical Center
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Menomonee Falls、Wisconsin、美国、53051
- Community Memorial Hospital Cancer Care Center
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Milwaukee、Wisconsin、美国、53226
- Medical College of Wisconsin Cancer Center
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Milwaukee、Wisconsin、美国、53295
- Veterans Affairs Medical Center - Milwaukee
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Milwaukee、Wisconsin、美国、53215
- Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
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West Allis、Wisconsin、美国、53227
- West Allis Memorial Hospital
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
男性
描述
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
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：支持治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：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.
|
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.
其他名称：
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.
|
|
有源比较器：Control
Vitamin D and calcium supplement everyday for 3 years in addition to concurrent radiation therapy and LHRH therapy.
|
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.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Freedom From Any Bone Fracture (FABF) Rate at Three Years
大体时间：From randomization to 3 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
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Percent Change in Bone Mineral Density at 3 Years
大体时间：Baseline, 3 years from start of treatment
|
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.
|
Baseline, 3 years from start of treatment
|
|
Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 Years
大体时间：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.
|
Baseline, 3 years from start of treatment
|
|
Utility of the Use of Bisphosphonates as Assessed by Quality-adjusted Survival
大体时间：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.
|
From pre-treatment to 3 years from start of treatment
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Colleen A. Lawton, MD、Medical College of Wisconsin
- 学习椅：Matthew R. Smith, MD、Massachusetts General Hospital
- 学习椅：Margaret Chamberlain-Wilmoth, PhD, MSS, RN、Carolinas Medical Center - University
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2006年3月1日
初级完成 (实际的)
2014年11月1日
研究完成 (实际的)
2014年11月1日
研究注册日期
首次提交
2006年5月23日
首先提交符合 QC 标准的
2006年5月23日
首次发布 (估计)
2006年5月25日
研究记录更新
最后更新发布 (实际的)
2017年11月29日
上次提交的符合 QC 标准的更新
2017年10月23日
最后验证
2017年10月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.