Zoledronate, Vitamin D, and Calcium With or Without Strontium 89 or Samarium 153 in Preventing or Delaying Bone Problems in Patients With Bone Metastases From Prostate Cancer, Lung Cancer, or Breast Cancer

Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases From Lung, Breast, and Prostate Cancer

RATIONALE: Zoledronate, vitamin D and calcium may prevent or delay bone pain and other symptoms caused by bone metastases. It is not yet known whether giving zoledronate together with vitamin D and calcium is more effective with or without strontium 89 or samarium 153 in treating patients with bone metastases from prostate cancer, lung cancer, or breast cancer.

PURPOSE: This randomized phase III trial is studying zoledronate, vitamin D, and calcium to see how well they work compared to zoledronate, vitamin D, calcium, and either strontium 89 or samarium 153 in preventing or delaying bone problems in patients with bone metastases from prostate cancer, lung cancer, or breast cancer.

Study Overview

• Status: Completed
• Conditions: Pain; Breast Cancer; Lung Cancer; Prostate Cancer; Metastatic Cancer
• Intervention / Treatment: Dietary supplement: Calcium; Dietary supplement: Vitamin D; Drug: zoledronic acid; Drug: Sm-153; Radiation: Sr-89

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of zoledronate, vitamin D, and calcium with or without strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium, in terms of preventing or delaying the time to development of malignant skeletal-related events (SREs) (defined as a pathological bone fracture, spinal cord compression, surgery to bone, or radiation to bone) in patients with bone metastases secondary to prostate, lung, or breast cancer.

Secondary

• Compare the rate of SREs at 1 year in patients treated with these regimens.
• Compare overall survival of patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.
• Compare the effect of these regimens on pain control in these patients.
• Evaluate resource utilization and cost effectiveness of these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to primary disease site (prostate vs breast vs lung) and number of bone metastases (≤ 2 vs > 2). Patients are randomized to 1 of 2 treatment arms.

Quality of life and pain are assessed at baseline and then at 1, 3, 6, and 12 months from start of protocol treatment.

After completion of study treatment, patients are followed every 6 months.

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Providence Cancer Center at Providence Hospital
  • California
    • Burbank, California, United States, 91505
      • Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
    • Carmichael, California, United States, 95608
      • Mercy Cancer Center at Mercy San Juan Medical Center
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Pomona, California, United States, 91767
      • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
    • Roseville, California, United States, 95661
      • Radiation Oncology Center - Roseville
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • Travis Air Force Base, California, United States, 94535-1800
      • General Robert Huyser Cancer Center at David Grant Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Integrated Community Oncology Network at Southside Cancer Center
    • Jacksonville, Florida, United States, 32258
      • Baptist Medical Center South
    • Jacksonville Beach, Florida, United States, 32250
      • Integrated Community Oncology Network
    • Miami, Florida, United States, 33133
      • Miami Cancer Center at Mercy Hospital
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Orange Park, Florida, United States, 32073
      • Integrated Community Oncology Network - Orange Park
    • Palatka, Florida, United States, 32177
      • Florida Cancer Center - Palatka
    • Panama City, Florida, United States, 32401
      • Bay Medical
    • Saint Augustine, Florida, United States, 32086
      • Flagler Cancer Center
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
    • Gainesville, Georgia, United States, 30501
      • Northeast Georgia Medical Center
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Downers Grove, Illinois, United States, 60515-1500
      • Good Samaritan Cancer Care Center at Advocate Good Samaritan Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care Center at Ingalls Memorial Hospital
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Park Ridge, Illinois, United States, 60068-1174
      • Advocate Lutheran General Cancer Care Center
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Springfield, Illinois, United States, 62702
      • Cancer Institute at St. John's Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Goshen, Indiana, United States, 46526
      • Center for Cancer Care at Goshen General Hospital
    • Muncie, Indiana, United States, 47303-3499
      • Cancer Center at Ball Memorial Hospital
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
  • Kansas
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40503-9985
      • Central Baptist Hospital
  • Louisiana
    • Alexandria, Louisiana, United States, 71315-3198
      • Tulane Cancer Center Office of Clinical Research
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Comprehensive Cancer Center at Central Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital Cancer Center
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • Hudner Oncology Center at Saint Anne's Hospital - Fall River
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Iron Mountain, Michigan, United States, 49801
      • Dickinson County Healthcare System
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Kansas City, Missouri, United States, 64108
      • Truman Medical Center - Hospital Hill
    • Springfield, Missouri, United States, 65804
      • St. John's Regional Health Center
    • Springfield, Missouri, United States, 65807
      • Hulston Cancer Center at Cox Medical Center South
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
  • Nebraska
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
  • New Jersey
    • Jamesburg, New Jersey, United States, 08831
      • Princeton Radiation Oncology Center
    • Marlton, New Jersey, United States, 08053
      • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
    • Princeton, New Jersey, United States, 08540-3298
      • University Medical Center at Princeton
    • Vineland, New Jersey, United States, 08360
      • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Cancer Center
  • New York
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Canandaigua, New York, United States, 14424
      • Sands Cancer Center
    • Plattsburgh, New York, United States, 12901
      • Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
    • Rochester, New York, United States, 14621
      • Lipson Cancer and Blood Center at Rochester General Hospital
    • Rochester, New York, United States, 14626
      • University Radiation Oncology at Parkridge Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Cancercare Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Alliance, Ohio, United States, 44601
      • Radiation Oncology Center
    • Barberton, Ohio, United States, 44203
      • Barberton Citizens Hospital
    • Canton, Ohio, United States, 44708
      • Mercy Cancer Center at Mercy Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45420
      • CCOP - Dayton
    • Franklin, Ohio, United States, 45005-1066
      • Middletown Regional Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Mansfield, Ohio, United States, 44903
      • MedCentral - Mansfield Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Care Center, Incorporated
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Wright-Patterson Air Force Base, Ohio, United States, 45433-5529
      • United States Air Force Medical Center - Wright-Patterson
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Rosenfeld Cancer Center at Abington Memorial Hospital
    • Beaver, Pennsylvania, United States, 15009
      • UPMC Cancer Center at Beaver Medical Center
    • Clairton, Pennsylvania, United States, 15025
      • UPMC Cancer Center at Jefferson Regional Medical Center
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Center - Arnold Palmer Pavilion
    • Johnstown, Pennsylvania, United States, 15901
      • UPMC Cancer Center at the John P. Murtha Pavilion
    • McKeesport, Pennsylvania, United States, 15132
      • UPMC Cancer Center at UPMC McKeesport
    • Moon, Pennsylvania, United States, 15108
      • UPMC - Moon
    • Natrona Heights, Pennsylvania, United States, 15065
      • UPMC Cancer Center - Natrona Heights
    • New Castle, Pennsylvania, United States, 16105
      • Jameson Memorial Hospital - North Campus
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Cancer Center at UPMC Presbyterian
    • Pittsburgh, Pennsylvania, United States, 15213-2582
      • UPMC - Shadyside
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Cancer Center at Magee-Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC Cancer Center at UPMC St. Margaret
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC Cancer Center at UPMC Passavant
    • Pittsburgh, Pennsylvania, United States, 15243
      • UPMC Cancer Center - Upper St. Clair
    • Seneca, Pennsylvania, United States, 16346
      • UPMC Cancer Center at UPMC Northwest
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
    • Uniontown, Pennsylvania, United States, 15401
      • UPMC Cancer Center - Uniontown
    • Washington, Pennsylvania, United States, 15301
      • Washington Hospital Cancer Center
    • York, Pennsylvania, United States, 17405
      • York Cancer Center at Apple Hill Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
  • Utah
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • Washington
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Tacoma, Washington, United States, 98405-3004
      • Franciscan Cancer Center at St. Joseph Medical Center
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center at Tacoma General Hospital
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • Theda Care Cancer Institute
    • Green Bay, Wisconsin, United States, 54301
      • Bellin Memorial Hospital
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Riverview UW Cancer Center at Riverview Hospital
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically proven diagnosis of solid tumor malignancy of lung, breast, or prostate prior to registration;

2. Appropriate diagnosis for protocol entry, based upon the following minimum diagnostic workup:

   2.1 History/physical examination within 8 weeks prior to registration; 2.2 Bone scan within 4 weeks prior to registration; bone metastases must be visible on the scan. Other scanning modalities, such as magnetic resonance imaging (MRI), positron emission tomography (PET) 2.3 Dental evaluation according to the dental exam checklist (carried out by the investigator, the investigator's designee, or by a qualified dental professional [dental hygienist or dentist]), including history of dental surgery (e.g., extraction or implant) within 8 weeks prior to registration and recorded on the dental exam checklist; Note: If the patient has received prior oral bisphosphonate therapy and has had a prior dental evaluation within 8 weeks of registration, the evaluation should not be repeated.

   2.4 Complete blood count (CBC)/differential within 2 weeks prior to registration, with adequate bone marrow function defined as follows:

   • White blood cell count (WBC) ≥ 2400 cells/mm^3;
   • Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3;
   • Platelets ≥ 60,000 cells/mm3;
   • Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve the required hemoglobin is permitted).

   2.5 Serum creatinine < 3 mg/dL (265 μmol/L) within 2 weeks prior to registration; 2.6 Total bilirubin < 2.5 mg/dL (43 μmol/L) within 2 weeks prior to registration; 2.7 Pregnancy test (urine dipstick or serum) for women of childbearing potential within 2 weeks prior to registration;

3. ≥ 18 years of age;
4. Zubrod performance status 0-2 for patients with breast or prostate primaries; Zubrod performance status 0-1 for patients with lung primaries;
5. Patients receiving systemic chemotherapy or hormonal therapy are eligible for this study. See Sections 6.0 and 7.0 for further details. Note: All patients must complete external beam radiation therapy ≥ 14 days prior to registration. If patients have undergone CyberKnife treatment, treatment must be completed ≥ 14 days prior to registration.
6. Patients may have received prior oral bisphosphonate therapy, such as Fosamax® or similar medications. Duration of bisphosphonate treatment prior to study entry must be documented, and all bisphosphonates other than the study drug must be discontinued prior to registration.
7. Women of childbearing potential and male participants must agree to practice an adequate means of birth control throughout their participation in the study.
8. Patient must sign study specific informed consent prior to study entry.

Exclusion Criteria

1. Patients with brain metastases and/or spinal cord compression are excluded. Note: Patients with no evidence of disease in the brain after treatment for brain metastases are eligible.
2. Patients with painful bone metastases are not permitted until these bone metastases are successfully treated (for example by external beam irradiation) prior to registration, and the patient has stable pain for at least 2 weeks after that treatment (Stable pain is defined for this study as a patient response of 1, 2, or 3 on Questions 4 and 5 of The Brief Pain Inventory (BPI).
3. Prior treatment with Strontium-89 or Samarium-153 for bone metastases.
4. Treatment for more than 6 months with IV bisphosphonates prior to study entry;
5. Treatment with calcitonin, mithramycin, or gallium nitrate within 2 weeks prior to registration

6. Severe, active co-morbidity, defined as follows:

   6.1 Evidence in the six months prior to study entry of uncontrolled congestive heart failure, hypertension refractory to treatment, or symptomatic coronary artery disease; 6.2 Current, active dental problems within 4 weeks of registration, including infection of the teeth or jawbone (maxilla or mandible); dental or fixture trauma; current or prior diagnosis of osteonecrosis of the jaw (ONJ); exposed bone in the mouth; or slow healing after dental procedures; 6.3 Dental surgery (e.g., extractions, implants) within 6 weeks of study entry and while receiving study treatment; for patients who require dental surgery, there are no data to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw (ONJ) [see Section 7.2.4].

   6.4 Acquired Immune Deficiency Syndrome (AIDS) based upon current Center for Disease Control (CDC) definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.

7. Pregnant or lactating patients are excluded, as treatment may be harmful to embryos and/or nursing infants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zoledronic acid; Zoledronic acid, vitamin D and calcium supplements.	Dietary supplement: Calcium; At least 500 mg of calcium (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.; Dietary supplement: Vitamin D; 400 IU of vitamin D (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.; Drug: zoledronic acid; 4 mg of Zoledronic acid intravenously once a month until the study doctor thinks it is in their best interest to stop.; Other Names: Zometa
Experimental: Zoledronic acid + Radiopharmaceuticals; Zoledronic acid, vitamin D and calcium supplements, plus Sr-89 or Sm-153.	Dietary supplement: Calcium; At least 500 mg of calcium (1 pill) by mouth daily until the study doctor thinks it is in their best interest to stop.; Drug: zoledronic acid; 4 mg of Zoledronic acid intravenously once a month until the study doctor thinks it is in their best interest to stop.; Other Names: Zometa; Drug: Sm-153; Single dose intravenously 1 mCi/kg body weight.; Other Names: Samarium-153; Radiation: Sr-89; Single dose intravenously 4 mCi.; Other Names: Strontium-89

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Development of a Malignant Skeletal-related Events (SRE)	Median time to development of a malignant skeletal related event (SRE), which is defined as a pathological bone fracture, spinal cord compression, surgery to bone or radiation to bone is estimated using Kaplan-Meier method. The time of failure was measured from date of randomization to the date of a documented SRE. The analysis was planned to occur after 257 SRE have been observed, unless the criteria for early stopping are met.	From randomization to last follow-up. Maximum follow-up at time of analysis was 80.1 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Experiencing a Skeletal-related Event (SRE) Within One Year	Skeletal-related events are defined as a pathological bone fracture, spinal cord compression, surgery to bone or radiation to bone.	From randomization to 1 year
Overall Survival	Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From randomization to last follow-up. Maximum follow-up at time of analysis was 101.7 months.
Change in Functional Assessment of Cancer Therapy - General (FACT-G) at One Year	The FACT-G is a validated 27-item measure in which a higher score represents higher quality of life (QOL). Physical, functional, social and emotional well-being subscale scores are added together to form the FACT-G total score. Responses range from 0=Not a lot to 4=Very much. Certain items must be reversed before being added, by subtracting the response from 4. Subscale items are added together, multiplied by the number of items in the subscale, then divided by the number of items answered to obtain subscale totals. Total score ranges from 0-108; physical, social and functional subscales from 0-28; emotional subscale from 0-24. 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. Change score at one year is calculated as one year score - baseline score with a positive change score indicating improvement in QOL.	Baseline and 1 year
Change in Brief Pain Inventory (BPI) at One Year	The Brief Pain Inventory (BPI) is a measurement tool for assessing clinical pain. The BPI assesses severity (pain at its "worst," "least," "average," and "now"), and interference (how much pain has interfered with seven daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Patients rate the severity of their pain and the degree to which their pain interferes with common dimensions of feeling and function on a scale of 0 to 10, with 0=no pain/interference and 10=interferes completely/worst pain imaginable.	Baseline and 1 year
Change in EuroQol-5 Dimension 3-level (EQ-5D-3L) at One Year	The EQ-5D-3L is a 2-part self-assessment questionnaire. First part is 5 items (mobility, self care, usual activities, pain/discomfort, anxiety/depression) each with 3 problem levels (1-none, 2-moderate, 3-extreme). The 5-item index score is transformed into a utility score between 0 (worst health state) and 1 (best health state). The 2nd part is a visual analogue scale (VAS) valuing current health state, measured on a 20-cm 10-point interval scale. Worst imaginable health state is scored as 0 at the bottom of the scale, and best imaginable health state is scored as 100 at the top. Change at one year is calculated as one-year score - baseline score with positive change indicating improved quality of life.	Baseline and 1 year

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Study Chair: Michael J. Seider, MD, PhD, FACR, Summa Center for Cancer Care at Akron City Hospital

Publications and helpful links

General Publications

• Seider MJ, Pugh SL, Langer C, Wyatt G, Demas W, Rashtian A, Clausen CL, Derdel JD, Cleary SF, Peters CA, Ramalingam A, Clarkson JE, Tomblyn M, Rabinovitch RA, Kachnic LA, Berk LB; NRG Oncology. Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid in the palliation of osteoblastic metastases from lung, breast, and prostate cancer: report of the NRG Oncology RTOG 0517 trial. Ann Nucl Med. 2018 Oct;32(8):553-560. doi: 10.1007/s12149-018-1278-4. Epub 2018 Aug 9.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2006
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): February 27, 2017

Study Registration Dates

• First Submitted: August 16, 2006
• First Submitted That Met QC Criteria: August 16, 2006
• First Posted (Estimate): August 17, 2006

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: May 31, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; recurrent non-small cell lung cancer; extensive stage small cell lung cancer; stage IV prostate cancer; recurrent prostate cancer; stage IV non-small cell lung cancer; pain; bone metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Breast Diseases; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Breast Neoplasms; Prostatic Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium; Zoledronic Acid
• Other Study ID Numbers: RTOG 0517; CDR0000491233; NCI-2009-00727 (Registry Identifier: CTRP (Clinical Trial Reporting Program))