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NCT00869206 · CITED IN SOURCE DOCUMENTS

Zoledronic Acid in Treating Patients With Metastatic Breast Cancer, Metastatic Prostate Cancer, or Multiple Myeloma With Bone Involvement

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2018-11-07

This randomized phase III trial studies two different schedules of zoledronic acid to compare how well they work in reducing bone-related complications in patients with breast cancer, prostate cancer, or multiple myeloma that has spread to other places in the body and have bone involvement. Bone-related complications are a major cause of morbidity in patients with metastatic prostate cancer, breast cancer, and multiple myeloma. Zoledronic acid may stop the growth of cancer cells in the bone and may help relieve some of the symptoms caused by bone metastases. It is not yet known whether giving zoledronic acid more or less frequently is more effective in treating patients with metastatic cancer that has spread to the bone.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Percentage of Participants With at Least One Skeletal-related Event (SRE) Within 2 Years After Randomization

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outcome · POSTED

Average Pain Intensity Score as Assessed by the Brief Pain Inventory (BPI) Questionnaire

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outcome · POSTED

Average ECOG Performance Status

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outcome · POSTED

Incidence of Osteonecrosis of the Jaw

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outcome · POSTED

Incidence of Renal Dysfunction

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outcome · POSTED

Skeletal Morbidity Rate

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outcome · POSTED

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Breast Cancer)

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outcome · POSTED

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Breast Cancer

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outcome · POSTED

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Prostate Cancer

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outcome · POSTED

Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Multiple Myeloma

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outcome · POSTED

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Prostate Cancer)

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outcome · POSTED

Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Multiple Myeloma)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Eligibility Criteria: * Histologic documentation of one of the following: breast adenocarcinoma, prostate adenocarcinoma or multiple myeloma * At least one site of bone metastasis or bone involvement by radiologic imaging including plain radiograph, computed tomography (CT), positron emission tomography (PET) scan, PET/CT scan, magnetic resonance imaging, bone scan, or skeletal survey; indeterminate lesions should be confirmed by a second imaging method * No prior treatment with IV bisphosphonates is allowed; prior treatment with oral bisphosphonates is allowed, but they must be discontinued prior to the initiation of protocol therapy * No prior treatment with denosumab * No prior treatment with radiopharmaceuticals; prior treatment with radioactive iodine is allowed; prostate cancer patients treated with brachytherapy are eligible * Prior radiation therapy to bone is allowed, provided that at least one site of bone metastasis has not been irradiated and radiation is completed prior to registration; there should be no plan for radiation therapy to non-irradiated sites of bone metastases * Prior adjuvant and metastatic chemotherapy, biologic therapy, and endocrine therapy is allowed * No current treatment with investigational agent(s) * Patients with known brain metastases are not eligible; patients who develop brain metastases during the study will be allowed to continue treatment as assigned * Not pregnant and not nursing * ECOG performance status 0-2 * Calculated creatinine clearance \>= 30 mL/min * Corrected serum calcium \>= 8.0 mg/dL (2.00 mmol/L) and \< 11.6 mg/dL (2.90 mmol/L) \* Corrected serum calcium should be calculated using standard institutional practices
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive zoledronic acid IV over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: zoledronic acid
    label
    Arm I (zoledronic acid every 4 weeks)
    type
    EXPERIMENTAL
  2. description
    Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: zoledronic acid
    label
    Arm II (zoledronic acid every 12 weeks)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I (zoledronic acid every 4 weeks)
    2. Arm II (zoledronic acid every 12 weeks)
    description
    Given IV
    name
    zoledronic acid
    type
    DRUG
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
SUPPORTIVE_CARE
Enrollment
count
1822
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion of patients who would have experienced at least one skeletal related event within 24 months after randomization.
    measure
    Percentage of Participants With at Least One Skeletal-related Event (SRE) Within 2 Years After Randomization
    time Frame
    2 years
secondary Outcomes
  1. description
    To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted for the mean interference score. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. The score of the BPI questionnaire ranges from 0 being no pain to 10 being the most pain. The average score is reported for each arm below.
    measure
    Average Pain Intensity Score as Assessed by the Brief Pain Inventory (BPI) Questionnaire
    time Frame
    from baseline up to 2 years
  2. description
    To compare functional status (ECOG performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The change scores were evaluated in a general linear model with repeated measures for treatment effect and the time trend with patient-specific characteristics being adjusted. Specifically the difference in score change per 4 weeks for Arm I using Arm II as the reference is reported. ECOG performance status is a measurement of a patients disability ranging from 0, fully active and able to carry out all pre disease performance without restriction, to 5, dead. The average performance status is reported below by arm.
    measure
    Average ECOG Performance Status
    time Frame
    from baseline up to 2 years
  3. description
    To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of participants with osteonecrosis is reported here.
    measure
    Incidence of Osteonecrosis of the Jaw
    time Frame
    from baseline up to 2 years
  4. description
    To compare the incidence of renal dysfunction of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The percentage of patients with renal dysfunction, defined as grade 3 or grade 4 increased creatinine (Common Terminology Criteria for Adverse Events version 3.0), will be reported here.
    measure
    Incidence of Renal Dysfunction
    time Frame
    from baseline up to 2 years
  5. description
    To compare the skeletal morbidity rate, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing.
    measure
    Skeletal Morbidity Rate
    time Frame
    from baseline up to 2 years
  6. description
    To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high \& low CTX values by arm will be reported here.
    measure
    Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Breast Cancer)
    time Frame
    from baseline up to 2 years
  7. description
    To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with breast cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.
    measure
    Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Breast Cancer
    time Frame
    from baseline up to 24 months
  8. description
    To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with prostate cancer, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.
    measure
    Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Prostate Cancer
    time Frame
    from baseline up to 24 months
  9. description
    To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization.
    measure
    Proportion of Patients Having at Least One SRE Within 24 Months After Randomization for the Subgroups of Patients With Multiple Myeloma
    time Frame
    from baseline up to 24 months
  10. description
    To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high \& low CTX values by arm will be reported here.
    measure
    Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Prostate Cancer)
    time Frame
    from baseline up to 24 months
  11. description
    To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. The number of patients with high \& low CTX values by arm will be reported here.
    measure
    Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Multiple Myeloma)
    time Frame
    from baseline up to 24 months
Full study description
brief Summary
This randomized phase III trial studies two different schedules of zoledronic acid to compare how well they work in reducing bone-related complications in patients with breast cancer, prostate cancer, or multiple myeloma that has spread to other places in the body and have bone involvement. Bone-related complications are a major cause of morbidity in patients with metastatic prostate cancer, breast cancer, and multiple myeloma. Zoledronic acid may stop the growth of cancer cells in the bone and may help relieve some of the symptoms caused by bone metastases. It is not yet known whether giving zoledronic acid more or less frequently is more effective in treating patients with metastatic cancer that has spread to the bone.
detailed Description
PRIMARY OBJECTIVES: I. To determine whether every-12-week therapy with zoledronic acid is not inferior to every-4-week therapy for patients with metastatic breast cancer, metastatic prostate cancer, or multiple myeloma involving bone, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization. SECONDARY OBJECTIVES: I. To compare pain scores (Brief Pain Inventory) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. II. To compare the functional status (Eastern Cooperative Oncology Group \[ECOG\] performance status) of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. III. To compare the incidence of osteonecrosis of the jaw in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. IV. To compare the incidence of renal dysfunction in patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. V. To compare the skeletal morbidity rate of these patients, defined as the number of skeletal-related events per year, of patients receiving every 12 week dosing to those receiving every 4 week dosing. VI. To compare the suppression of serum markers of bone resorption of patients with metastatic breast cancer, metastatic prostate cancer, or myeloma involving bone receiving every 12 week dosing of zoledronic acid to those receiving every 4 week dosing. VII. To determine whether every 12 week therapy with zoledronic acid is not inferior to every-4-week therapy for each subgroup of patients with either breast cancer, prostate cancer, or multiple myeloma, as measured by the proportion who experience at least one skeletal related event within 24 months after randomization. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive zoledronic acid intravenously (IV) over at least 15 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive zoledronic acid IV over at least 15 minutes every 12 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 weeks for 2 years from registration.
Source references
references
  1. citation
    Chen F, Zhao B, Tian Y, Liu Q, Zhang B. Metabolic reprogramming on breast cancer stem Cells: Proliferation and self-renewal, epithelial-mesenchymal transition (EMT), and drug resistance. Biochem Biophys Res Commun. 2025 Aug 8;774:152079. doi: 10.1016/j.bbrc.2025.152079. Epub 2025 May 23.
    pmid
    40446745
    type
    DERIVED
  2. citation
    Himelstein AL, Foster JC, Khatcheressian JL, Roberts JD, Seisler DK, Novotny PJ, Qin R, Go RS, Grubbs SS, O'Connor T, Velasco MR Jr, Weckstein D, O'Mara A, Loprinzi CL, Shapiro CL. Effect of Longer-Interval vs Standard Dosing of Zoledronic Acid on Skeletal Events in Patients With Bone Metastases: A Randomized Clinical Trial. JAMA. 2017 Jan 3;317(1):48-58. doi: 10.1001/jama.2016.19425.
    pmid
    28030702
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        > <p id="_1732" tabindex="-1">The optimal dosing schedule for zoledronate was studied in <a href="/clinicaltrials/NCT00869206">CALGB-70604</a> (Alliance; NCT00869206), which randomly assigned 1,822 patients, 855 of whom had metastatic breast cancer, to receive zoledronic acid every 4 weeks or every 12 weeks.[<a href="#cit/s
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      1. context
        Updated: April 25, 2025
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        April 25, 2025

    Preserved source evidence · Not medical advice