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

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:

Genetics Home Reference related topics: breast cancer multiple myeloma prostate cancer

MedlinePlus related topics: Breast Cancer Cancer Multiple Myeloma Prostate Cancer

Drug Information available for: Zoledronic acid

Genetic and Rare Diseases Information Center resources: Multiple Myeloma Bone Cancer

U.S. FDA Resources

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 (Adult, Senior)
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

National Cancer Institute (NCI)

Investigators


Study Chair:	Andrew L. Himelstein, MD	Helen F. Graham Cancer Center at Christiana Hospital

More Information


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 1, 2016
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:


Multiple Myeloma Neoplasms, Plasma Cell Adenocarcinoma Neoplasms Neoplasms, Second Primary Bone Neoplasms Bone Marrow Diseases Neoplasm Metastasis 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 Neoplasms by Site Bone Diseases Musculoskeletal Diseases Neoplastic Processes Pathologic Processes Zoledronic acid Diphosphonates Bone Density Conservation Agents Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016