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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00869206
First received: March 24, 2009
Last updated: July 23, 2015
Last verified: July 2015
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Proportion of patients with at least one skeletal-related event (SRE) within 2 years after randomization [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pain intensity score as assessed by the Brief Pain Inventory (BPI) questionnaire [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • ECOG performance status [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of osteonecrosis of the jaw [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Incidence of renal dysfunction [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Skeletal morbidity rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Bone turnover assessed by serum N-telopeptide (NTX) levels [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Proportion of patients having at least one SRE within 24 months after randomization for the subgroups of patients with breast cancer, prostate cancer, and multiple myeloma [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 1758
Study Start Date: March 2009
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869206

  Show 504 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Andrew L. Himelstein, MD Helen F. Graham Cancer Center at Christiana Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00869206     History of Changes
Other Study ID Numbers: CALGB-70604, CDR0000637947, NCI-2009-01102, U10CA037447
Study First Received: March 24, 2009
Last Updated: July 23, 2015
Health Authority: United States: Institutional Review Board

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:
Adenocarcinoma
Bone Marrow Diseases
Bone Neoplasms
Breast Neoplasms
Multiple Myeloma
Neoplasm Metastasis
Neoplasms
Neoplasms, Plasma Cell
Neoplasms, Second Primary
Blood Protein Disorders
Bone Diseases
Breast Diseases
Carcinoma
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Musculoskeletal Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplastic Processes
Paraproteinemias
Pathologic Processes
Skin Diseases
Vascular Diseases
Diphosphonates

ClinicalTrials.gov processed this record on August 27, 2015