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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00365105
• Other study ID #: RTOG 0517
• Secondary ID: CDR0000491233NCI
• Status: Completed
• Phase: Phase 3
• Start date: July 11, 2006
• Est. completion date: February 27, 2017

Study information

• Verified date: May 2019
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: February 27, 2017
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Lung Cancer
• Lung Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis
• Pain
• Prostate Cancer
• Prostatic Neoplasms

Intervention

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.
• 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.
• Sm-153
Single dose intravenously 1 mCi/kg body weight.

Radiation:
• Sr-89
Single dose intravenously 4 mCi.

Locations

Country	Name	City	State
United States	Rosenfeld Cancer Center at Abington Memorial Hospital	Abington	Pennsylvania
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	New Mexico Cancer Center	Albuquerque	New Mexico
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Radiation Oncology Center	Alliance	Ohio
United States	McFarland Clinic, PC	Ames	Iowa
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Theda Care Cancer Institute	Appleton	Wisconsin
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	UPMC Cancer Center at Beaver Medical Center	Beaver	Pennsylvania
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	New York Methodist Hospital	Brooklyn	New York
United States	Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center	Burbank	California
United States	Sands Cancer Center	Canandaigua	New York
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	UPMC Cancer Center at Jefferson Regional Medical Center	Clairton	Pennsylvania
United States	CCOP - Columbus	Columbus	Ohio
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Good Samaritan Cancer Care Center at Advocate Good Samaritan Hospital	Downers Grove	Illinois
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts
United States	St. Francis Hospital	Federal Way	Washington
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Center for Cancer Care at Goshen General Hospital	Goshen	Indiana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
United States	UPMC Cancer Center - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	CCOP - Greenville	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois
United States	Veterans Affairs Medical Center - Hines	Hines	Illinois
United States	Cape Cod Hospital	Hyannis	Massachusetts
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network at Southside Cancer Center	Jacksonville	Florida
United States	Integrated Community Oncology Network	Jacksonville Beach	Florida
United States	Princeton Radiation Oncology Center	Jamesburg	New Jersey
United States	UPMC Cancer Center at the John P. Murtha Pavilion	Johnstown	Pennsylvania
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Central Maine Comprehensive Cancer Center at Central Maine Medical Center	Lewiston	Maine
United States	Central Baptist Hospital	Lexington	Kentucky
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	MedCentral - Mansfield Hospital	Mansfield	Ohio
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	UPMC Cancer Center at UPMC McKeesport	McKeesport	Pennsylvania
United States	Miami Cancer Center at Mercy Hospital	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Trinity CancerCare Center	Minot	North Dakota
United States	Providence Cancer Center at Providence Hospital	Mobile	Alabama
United States	UPMC - Moon	Moon	Pennsylvania
United States	Cancer Center at Ball Memorial Hospital	Muncie	Indiana
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	UPMC Cancer Center - Natrona Heights	Natrona Heights	Pennsylvania
United States	Jameson Memorial Hospital - North Campus	New Castle	Pennsylvania
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Integrated Community Oncology Network - Orange Park	Orange Park	Florida
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Bay Medical	Panama City	Florida
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	UPMC - Shadyside	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center - Upper St. Clair	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at Magee-Womens Hospital	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC Passavant	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC St. Margaret	Pittsburgh	Pennsylvania
United States	Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York
United States	Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center	Pomona	California
United States	University Medical Center at Princeton	Princeton	New Jersey
United States	Good Samaritan Cancer Center	Puyallup	Washington
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Lipson Cancer and Blood Center at Rochester General Hospital	Rochester	New York
United States	University Radiation Oncology at Parkridge Hospital	Rochester	New York
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	CCOP - Northwest	Tacoma	Washington
United States	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington
United States	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida
United States	General Robert Huyser Cancer Center at David Grant Medical Center	Travis Air Force Base	California
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	UPMC Cancer Center - Uniontown	Uniontown	Pennsylvania
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	St. John Macomb Hospital	Warren	Michigan
United States	Washington Hospital Cancer Center	Washington	Pennsylvania
United States	CCOP - Wichita	Wichita	Kansas
United States	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Cancer Treatment Center	Wooster	Ohio
United States	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Air Force Base	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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