Zoledronic Acid Administration to Metastatic Breast Cancer Patients With Non-symptomatic Bone Lesions

Study Overview
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Brief Summary
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This is an open-label, randomized, multicenter phase III trial to assess the efficacy of early administration of zoledronate versus observation in delaying bone-related symptoms in metastatic breast cancer patients.

Detailed Description
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Patients will be randomised to receive 4 mg zoledronate every 3-4 weeks versus observation until bone-related symptoms appear, or up to 12 months. One hundred twelve patients per treatment arm will be enrolled in the study. Once bone-related symptoms appear, study participation is over. During the study, the following will be assessed: quality of life, performance status, pain rating, analgesic administration and adverse events The principal objective is the delay in bone-related symptoms in those patients with early zoledronate administration.

Official Title
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Multicenter, Open-label, Randomized Phase III Trial for Administration of Zoledronate to Breast Cancer Metastatic Patients With Non-symptomatic Bone Lesions

Conditions
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Breast Cancer, Neoplasm Metastasis

Intervention / Treatment
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* Drug: Zoledronic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent. Age >= 18 years old. Metastatic breast cancer patients with lytic, sclerotic or mixed bone lesions. Non-symptomatic bone lesions, defined as pain absence, lack of bone complications (fracture, hypercalcemia, Central Nervous System (CNS) compression), no need of analgesic chronic administration for bone disease. A maximum of two chemotherapy lines for metastatic disease. A maximum of two hormone therapy lines for metastatic disease. Normal, minimally altered renal function (serum creatinine < 1.5 x Upper Normal Limit (UNL)). Normal serum calcium levels. Performance status 0,1 (World Health Organization (WHO)). Negative pregnancy test before study recruitment. Exclusion Criteria: Previous treatment with bisphosphonates or raloxifene in the 30 days prior to randomization. Metastasis in CNS. History of hypersensitivity to bisphosphonates. Pregnant or lactating women. Third chemotherapy line for metastatic disease. Third hormone therapy line for metastatic disease. Males.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Zoledronic acid 4 mg<br>Zoledronate 4 mg every 3 or 4 weeks. This arm will receive study treatment from the time of entry into the trial, until the appearance of the symptoms of bone metastases (or a maximum period of 12 months, whichever occurs first). | Drug: Zoledronic acid<br> <br> * Other names: Zometa;|
| No Intervention: Arm B: Observation<br>Patients will not receive any treatment with bisphosphonates until the time of onset of symptoms (or a maximum period of 12 months, whichever occurs sooner). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first bone metastases | The main variable of evaluation is the time until the appearance of first bone metastases. | Up to disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life per treatment arm | Quality of Life (QoL) will be measured with Short Form (SF)-36 questionnaire and Short questionnaire for the evaluation of pain since baseline visit and during all treatment period delivered to the patient before the start of each visit. | Up to disease progression | 
| The Number of Participants Who Experienced Adverse Events (AE) | Safety will be assessed by standard clinical and laboratory tests. Adverse events grade will be defined by the NCI CTCAE. | Through study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-symptomatic bone metastases.