BACKGROUND A substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement. Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects. METHODS/DESIGN CARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy. DISCUSSION The CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit. TRIAL REGISTRATION ISRCTN, ISRCTN92755158, Registered on 17 February 2016.

中文翻译：

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CApecitabine加Radium-223（Xofigo™）用于BONE转移的乳腺癌患者（CARBON）：IB / IIA期随机对照试验的研究方案。

背景技术相当大比例的乳腺癌患者发展成转移性疾病，全球每年有超过45万死亡。骨是最常见的转移性疾病首发部位，占所有首次复发的40％，晚期疾病的患者中有70％会发展为骨骼受累。骨转移的治疗目前集中在症状缓解以及骨骼并发症的预防和治疗上。然而，仍然需要针对患有骨转移的患者的进一步治疗选择。将全身疗法与骨靶向药物（如Radium-223）结合使用，可以提供一种有效的治疗方法，同时具有最小的其他副作用。方法/设计碳素是英国的开放标签，一项多中心研究，包括一个初始安全阶段，以建立将每周六次给药的镭223与口服卡培他滨联合使用的可行性和安全性，然后进行随机扩展阶段以进一步表征安全性并提供初步估计功效。讨论CARBON研究很重要，因为该结果将首次评估晚期乳腺癌中化疗联合镭223的使用。如果结果发现可接受的毒性反应速率和骨转换标志物减少，则需要在II / III期进行进一步的工作以评估疗效和临床获益。试用注册号ISRCTN，ISRCTN92755158，于2016年2月17日注册。