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

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

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.

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.

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.