Study Comparing Full-dose Radiotherapy Versus Reduced Dose in the Management of Bone Metastasis in Patients With Breast Cancer Receiving Zoledronic Acid

Study Comparing Full-dose Radiotherapy Versus Reduced Dose in the Management of Bone Metastasis in Patients With Breast Cancer Receiving Zoledronic Acid

The aim of this prospective, randomized, open-label, multicentric clinical study is to assess the effícacy and tolerability of zoledronic acid 4 mg IV infused over 15 minutes every 4 weeks for a total of 6 infusions, in combination with standard or reduced dose radiotherapy in patients with breast cancer and metastatic bone disease associated with pain.

Inclusion Criteria:

• Female patients aged ≥ 18 years.
• Histologically confirmed diagnosis of breast cancer with at least one bone metastases.
• Radiologically documented solitary or multiple osteolytic or osteoblastic lesions in axial skeleton or in the extremities in which radiotherapy is indicated.
• Pain and/or analgesic score ≥ 3 (see section 3.5.2) at the bone site to be irradiated.
• ECOG performance status ≤ 2.
• Life expectancy more than 6 months.

Exclusion Criteria:

• Patients in whom the target lesion(s) is not detectable by conventional techniques (i.e. X-rays MRI or CT scan).
• Presence of pathological fracture in the target lesion(s).
• Prior irradiation of the painful area(s) to be irradiated.
• Known hypersensitivity to zoledronic acid or other biphosphonates.
• Previous treatment with bisphosphonates for the current disease; any treatment with biphosphonates for other indications should anyway have been discontinued at least two years before randomization into the study.
• Skeleton-related complications (e.g., pathological fractures, orthopedic intervention to treat or stabilize an osteolytic defect, spinal cord compression) during the last 3 weeks prior to the first infusion of trial medication.
• Change in anticancer therapy within the 2 weeks prior to screening assessments and/or test treatment start.
• Patients with severe renal function (serum creatinine > 400 umol/l or > 4.5 mg/dl or calculated creatinine clearance ≤ 30 ml/minute) or with prior renal transplantation. Creatinine clearance will be calculated using the following formula:

Creatinine clearance = (140-age[yr])(body weight [kg]) x 0.85 (72) (serum creatinine [mg/dL]) or Creatinine clearance = (140-age[yr])(body weight [kg]) x 0.85 (0.814) (serum creatinine [µmol/L])

• Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/L).
• Patients with clinically symptomatic brain metastases
• Bone metabolism disorder, e.g. Paget disease, primary hyperparathyroidism
• Serious intercurrent illness other than breast cancer that can interfere with the evaluation of the effect of the therapy.
• Pregnancy and lactation.
• Women of childbearing potential not on an effective form of contraception.
• Known history or present abuse of alcohol or drugs (accepted social alcohol usage will not exclude the patient)
• Patients who, in the opinion of the investigator, are unlikely to cooperate fully during the study.

Other protocol-defined inclusion/exclusion criteria may apply.