Efficacy and Tolerability of Zoledronic Acid With Radiotherapy in Pts With Advanced Osteolytic Bone Lesions

Evaluation of the Efficacy and Tolerability of Zoledronic Acid in Combination With Radiotherapy in Patients With Advanced Osteolytic Bone Lesions

It is the aim of this multicentric clinical study to assess the efficacy and tolerability of zoledronic acid in combination with radiotherapy in patients with advanced osteolytic bone lesions in terms of the reduction of pain and analgesic consumption.

Inclusion Criteria:

• Diagnosis of at least one cancer-related bone lesion in cancer patients, confirmed by X-ray, MRT or computer tomography
• Severity of pain ≥ 5 on item 3 of the BPI which is caused by the bone lesion(s) and requires radiotherapy
• Adequate liver function - serum total bilirubin concentration less than 1.5 x the upper limit of normal value
• Expected survival time ≥ 6 months
• If the patient is of child-bearing potential: negative pregnancy test at screening
• ECOG performance status of 0, 1 or 2.
• Written informed consent

Exclusion Criteria:

• Prior treatment with an oral bisphosphonate for more than 3 months or more than 3 intravenous (i.v.) bisphosphonate applications
• Bisphosphonate treatment within 6 months before study start
• Previous radiotherapy of the painful areas to be irradiated. An initiation of radiotherapy for the target area(s) up to 3 days at maximum prior to the first infusion is allowed.
• 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.
• Initiation of a new chemotherapeutic treatment regimen during the last 2 weeks prior to the first infusion of trial medication
• Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula: CrCl = [140-age (years)] x weight (kg) {x 0.85 for female patients} [72 x serum creatinine (mg/dL)]
• Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/L) or ≥ 12.0 mg/dl (3.00 mmol/L).
• Patients with clinically symptomatic brain metastases
• History of diseases with influence on bone metabolism such as Paget's disease and primary hyperparathyroidism
• Pregnancy and lactation
• Women of childbearing potential not on a medically recognized form of contraception (i.e., oral contraceptives or implants, intrauterine device [IUD], vaginal diaphragm or sponge, or condom with spermicide)
• Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
• Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)

Other protocol-defined inclusion/exclusion criteria may apply.