Clinical trial NCT00329797: Zoledronate in Preventing Osteoporosis and Bone Fractures in Patients With Locally Advanced Nonmetastatic Prostate Cancer Undergoing Radiation Therapy and Hormone Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoporosis
Prostate Cancer
Keywords: osteoporosis
adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-05-25
Enrollment: 109
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Zoledronate may prevent bone loss in patients with prostate cancer undergoing radiation therapy and hormone therapy. It is not yet known whether zoledronate is more effective than calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying zoledronate to see how well it works compared to calcium and vitamin D alone in preventing osteoporosis and bone fractures in patients with locally advanced nonmetastatic prostate cancer undergoing radiation therapy and hormone therapy.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Freedom From Any Bone Fracture (FABF) Rate at Three Years
timeFrame: From randomization to 3 years
Secondary outcomes:
measure: Percent Change in Bone Mineral Density at 3 Years
timeFrame: Baseline, 3 years from start of treatment
measure: Changes in the Functional Assessment of Cancer Therapy-General (FACT-G) at 3 Years
timeFrame: Baseline, 3 years from start of treatment
measure: Utility of the Use of Bisphosphonates as Assessed by Quality-adjusted Survival
timeFrame: From pre-treatment to 3 years from start of treatment
Other outcomes:
Locations:
city: Chico
country: United States
facility: Enloe Cancer Center at Enloe Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Pomona
country: United States
facility: Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
state: California
city: Roseville
country: United States
facility: Radiation Oncology Center - Roseville
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Colorado Springs
country: United States
facility: Penrose Cancer Center at Penrose Hospital
state: Colorado
city: Pueblo
country: United States
facility: St. Mary - Corwin Regional Medical Center
state: Colorado
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Arlington Heights
country: United States
facility: Northwest Community Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Cancer Care Center at Ingalls Memorial Hospital
state: Illinois
city: Olympia Fields
country: United States
facility: Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Goshen
country: United States
facility: Center for Cancer Care at Goshen General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Cancer Center at Methodist Hospital
state: Indiana
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Saint Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Cape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Las Vegas
country: United States
facility: University Medical Center of Southern Nevada
state: Nevada
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Reno
country: United States
facility: Renown Institute for Cancer at Renown Regional Medical Center
state: Nevada
city: Keene
country: United States
facility: Kingsbury Center for Cancer Care at Cheshire Medical Center
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cancer Institute of New Jersey at Cooper University Hospital - Camden
state: New Jersey
city: Vineland
country: United States
facility: Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
state: New Jersey
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: Binghamton
country: United States
facility: Lourdes Regional Cancer Center
state: New York
city: Brooklyn
country: United States
facility: Veterans Affairs Medical Center - Brooklyn
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina - Raleigh
state: North Carolina
city: Wilson
country: United States
facility: Wilmed Radiation Oncology Services
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
state: Ohio
city: West Chester
country: United States
facility: Precision Radiotherapy at University Pointe
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Abington
country: United States
facility: Rosenfeld Cancer Center at Abington Memorial Hospital
state: Pennsylvania
city: Bryn Mawr
country: United States
facility: Bryn Mawr Hospital
state: Pennsylvania
city: Gettysburg
country: United States
facility: Adams Cancer Center
state: Pennsylvania
city: Paoli
country: United States
facility: Cancer Center of Paoli Memorial Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center at Apple Hill Medical Center
state: Pennsylvania
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Ogden
country: United States
facility: Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center - North
state: Vermont
city: Norfolk
country: United States
facility: Sentara Cancer Institute at Sentara Norfolk General Hospital
state: Virginia
city: Portsmouth
country: United States
facility: Naval Medical Center - Portsmouth
state: Virginia
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Appleton
country: United States
facility: Theda Care Cancer Institute
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital Cancer Care Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee
state: Wisconsin
city: West Allis
country: United States
facility: West Allis Memorial Hospital
state: Wisconsin
city: Victoria
country: Canada
facility: British Columbia Cancer Agency - Vancouver Island Centre
state: British Columbia
city: St. John's
country: Canada
facility: Doctor H. Bliss Murphy Cancer Centre
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: Thunder Bay
country: Canada
facility: Cancer Care Program at Thunder Bay Regional Health Sciences
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre at Pasqua Hospital
state: Saskatchewan
Study officials:
affiliation: Medical College of Wisconsin
name: Colleen A. Lawton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Matthew R. Smith, MD
role: STUDY_CHAIR
affiliation: Carolinas Medical Center - University
name: Margaret Chamberlain-Wilmoth, PhD, MSS, RN
role: STUDY_CHAIR
References: