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

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ClinicalTrials.gov Identifier: NCT00869206
Recruitment Status : Completed
First Posted : March 25, 2009
Results First Posted : November 7, 2018
Last Update Posted : November 7, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Study Description
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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.

Condition or disease Intervention/treatment Phase
Breast Adenocarcinoma DS Stage I Plasma Cell Myeloma DS Stage II Plasma Cell Myeloma Metastatic Malignant Neoplasm to the Bone Pain Musculoskeletal Complication Urinary Complications Drug: zoledronic acid Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1822 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Randomized, Phase III Study of Standard Dosing Versus Longer Dosing Interval of Zoledronic Acid in Metastatic Cancer
Study Start Date : March 2009
Actual Primary Completion Date : June 2014
Actual Study Completion Date : January 2017

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm I (zoledronic acid every 4 weeks)
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.
 Drug: zoledronic acid
Given IV
Experimental: Arm II (zoledronic acid every 12 weeks)
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.
 Drug: zoledronic acid
Given IV


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With at Least One Skeletal-related Event (SRE) Within 2 Years After Randomization [ Time Frame: 2 years ]
    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.


Secondary Outcome Measures :
  1. Average Pain Intensity Score as Assessed by the Brief Pain Inventory (BPI) Questionnaire [ Time Frame: from baseline up to 2 years ]
    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.

  2. Average ECOG Performance Status [ Time Frame: from baseline up to 2 years ]
    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.

  3. Incidence of Osteonecrosis of the Jaw [ Time Frame: from baseline up to 2 years ]
    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.

  4. Incidence of Renal Dysfunction [ Time Frame: from baseline up to 2 years ]
    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.

  5. Skeletal Morbidity Rate [ Time Frame: from baseline up to 2 years ]
    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.

  6. Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Breast Cancer) [ Time Frame: from baseline up to 2 years ]
    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.

  7. 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 ]
    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.

  8. 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 ]
    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.

  9. 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 ]
    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.

  10. Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Prostate Cancer) [ Time Frame: from baseline up to 24 months ]
    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.

  11. Bone Turnover Assessed by Serum C-telopeptide (CTX) Levels (Multiple Myeloma) [ Time Frame: from baseline up to 24 months ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00869206


Locations
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Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
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Study Chair: Andrew L. Himelstein, MD Helen F. Graham Cancer Center at Christiana Hospital
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00869206    
Other Study ID Numbers: CALGB-70604
CDR0000637947 ( Registry Identifier: NCI Physician Data Query )
NCI-2009-01102 ( Registry Identifier: NCI Clinical Trial Reporting Program )
U10CA037447 ( U.S. NIH Grant/Contract )
First Posted: March 25, 2009    Key Record Dates
Results First Posted: November 7, 2018
Last Update Posted: November 7, 2018
Last Verified: October 2018
Keywords provided by Alliance for Clinical Trials in Oncology:
pain
Prostate Adenocarcinoma
urinary complications
stage IV breast cancer
Recurrent Breast Carcinoma
stage IV prostate cancer
 recurrent prostate cancer
Recurrent Prostate Carcinoma
stage I multiple myeloma
stage II multiple myeloma
Refractory Plasma Cell Myeloma
bone metastases
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Adenocarcinoma
Neoplasms
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
 Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Zoledronic Acid
Bone Density Conservation Agents
Physiological Effects of Drugs