Clinical trial NCT00365105: 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
Official title: Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases From Lung, Breast, and Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lung Cancer
Metastatic Cancer
Pain
Prostate Cancer
Keywords: pain
bone metastases
extensive stage small cell lung cancer
recurrent breast cancer
stage IV breast cancer
recurrent non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent prostate cancer
stage IV prostate cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2006-08-17
Enrollment: 261
Sex: ALL
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, 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to Development of a Malignant Skeletal-related Events (SRE)
timeFrame: From randomization to last follow-up. Maximum follow-up at time of analysis was 80.1 months.
Secondary outcomes:
measure: Number of Patients Experiencing a Skeletal-related Event (SRE) Within One Year
timeFrame: From randomization to 1 year
measure: Overall Survival
timeFrame: From randomization to last follow-up. Maximum follow-up at time of analysis was 101.7 months.
measure: Change in Functional Assessment of Cancer Therapy - General (FACT-G) at One Year
timeFrame: Baseline and 1 year
measure: Change in Brief Pain Inventory (BPI) at One Year
timeFrame: Baseline and 1 year
measure: Change in EuroQol-5 Dimension 3-level (EQ-5D-3L) at One Year
timeFrame: Baseline and 1 year
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Providence Cancer Center at Providence Hospital
state: Alabama
city: Burbank
country: United States
facility: Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
state: California
city: Carmichael
country: United States
facility: Mercy Cancer Center at Mercy San Juan 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: Travis Air Force Base
country: United States
facility: General Robert Huyser Cancer Center at David Grant Medical Center
state: California
city: Fort Lauderdale
country: United States
facility: Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Jacksonville Beach
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network at Southside Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Baptist Medical Center South
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Center at Mercy Hospital
state: Florida
city: Orange Park
country: United States
facility: Integrated Community Oncology Network - Orange Park
state: Florida
city: Palatka
country: United States
facility: Florida Cancer Center - Palatka
state: Florida
city: Panama City
country: United States
facility: Bay Medical
state: Florida
city: Saint Augustine
country: United States
facility: Flagler Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Columbus
country: United States
facility: John B. Amos Cancer Center
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Arlington Heights
country: United States
facility: Northwest Community Hospital
state: Illinois
city: Downers Grove
country: United States
facility: Good Samaritan Cancer Care Center at Advocate Good Samaritan Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Cancer Care Center at Ingalls Memorial Hospital
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Cancer Care Center
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
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: Muncie
country: United States
facility: Cancer Center at Ball Memorial Hospital
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Lexington
country: United States
facility: Central Baptist Hospital
state: Kentucky
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Lewiston
country: United States
facility: Central Maine Comprehensive Cancer Center at Central Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: St. Agnes Hospital Cancer Center
state: Maryland
city: Fall River
country: United States
facility: Hudner Oncology Center at Saint Anne's Hospital - Fall River
state: Massachusetts
city: Hyannis
country: United States
facility: Cape Cod Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Saint Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Kansas City
country: United States
facility: Truman Medical Center - Hospital Hill
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
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: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Kearney
country: United States
facility: Good Samaritan Cancer Center at Good Samaritan Hospital
state: Nebraska
city: Jamesburg
country: United States
facility: Princeton Radiation Oncology Center
state: New Jersey
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
state: New Jersey
city: Princeton
country: United States
facility: University Medical Center at Princeton
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: Albuquerque
country: United States
facility: New Mexico Cancer Center
state: New Mexico
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Canandaigua
country: United States
facility: Sands Cancer Center
state: New York
city: Plattsburgh
country: United States
facility: Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center
state: New York
city: Rochester
country: United States
facility: Highland Hospital of Rochester
state: New York
city: Rochester
country: United States
facility: Lipson Cancer and Blood Center at Rochester General Hospital
state: New York
city: Rochester
country: United States
facility: University Radiation Oncology at Parkridge Hospital
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Minot
country: United States
facility: Trinity CancerCare Center
state: North Dakota
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: Alliance
country: United States
facility: Radiation Oncology Center
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Canton
country: United States
facility: Mercy Cancer Center at Mercy Medical Center
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Mansfield
country: United States
facility: MedCentral - Mansfield Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Wright-Patterson Air Force Base
country: United States
facility: United States Air Force Medical Center - Wright-Patterson
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Tulsa
country: United States
facility: Natalie Warren Bryant Cancer Center at St. Francis Hospital
state: Oklahoma
city: Abington
country: United States
facility: Rosenfeld Cancer Center at Abington Memorial Hospital
state: Pennsylvania
city: Beaver
country: United States
facility: UPMC Cancer Center at Beaver Medical Center
state: Pennsylvania
city: Clairton
country: United States
facility: UPMC Cancer Center at Jefferson Regional Medical Center
state: Pennsylvania
city: Dunmore
country: United States
facility: Northeast Radiation Oncology Center
state: Pennsylvania
city: Greensburg
country: United States
facility: UPMC Cancer Center - Arnold Palmer Pavilion
state: Pennsylvania
city: Johnstown
country: United States
facility: UPMC Cancer Center at the John P. Murtha Pavilion
state: Pennsylvania
city: McKeesport
country: United States
facility: UPMC Cancer Center at UPMC McKeesport
state: Pennsylvania
city: Moon
country: United States
facility: UPMC - Moon
state: Pennsylvania
city: Natrona Heights
country: United States
facility: UPMC Cancer Center - Natrona Heights
state: Pennsylvania
city: New Castle
country: United States
facility: Jameson Memorial Hospital - North Campus
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - Shadyside
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at Magee-Womens Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC Presbyterian
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC St. Margaret
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at UPMC Passavant
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Center - Upper St. Clair
state: Pennsylvania
city: Seneca
country: United States
facility: UPMC Cancer Center at UPMC Northwest
state: Pennsylvania
city: State College
country: United States
facility: Mount Nittany Medical Center
state: Pennsylvania
city: Uniontown
country: United States
facility: UPMC Cancer Center - Uniontown
state: Pennsylvania
city: Washington
country: United States
facility: Washington Hospital Cancer Center
state: Pennsylvania
city: York
country: United States
facility: York Cancer Center at Apple Hill Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
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: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Federal Way
country: United States
facility: St. Francis Hospital
state: Washington
city: Puyallup
country: United States
facility: Good Samaritan Cancer Center
state: Washington
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Tacoma
country: United States
facility: Franciscan Cancer Center at St. Joseph Medical Center
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center at Tacoma General Hospital
state: Washington
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: Bellin Memorial Hospital
state: Wisconsin
city: Wisconsin Rapids
country: United States
facility: Riverview UW Cancer Center at Riverview Hospital
state: Wisconsin
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: Summa Center for Cancer Care at Akron City Hospital
name: Michael J. Seider, MD, PhD, FACR
role: STUDY_CHAIR
References:
citation: 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.