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

Study Overview
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Brief Summary
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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.

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

Conditions
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Breast Cancer With Metastatic Bone Disease

Intervention / Treatment
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* Drug: Zoledronic acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: ZOL446 Standard radiotherapy dosage<br> | Drug: Zoledronic acid<br> <br> * Other names: ZOL446;|
| Experimental: ZOL446 Low radiotherapy dosage<br> | Drug: Zoledronic acid<br> <br> * Other names: ZOL446;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients showing complete response in bone pain palliation without having any analgesic treatment |  | day 5, 12, 29; week 8, 12, 16, 20 & 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zoledronic acid, Radiotherapy, Bone pain, Breast cancer