CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases (CARBON): study protocol for a phase IB/IIA randomised controlled trial

Abstract

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.

Radium-223 as an Additional Therapeutic Strategy in Highly Selected Patients With Metastatic Breast Cancer: A Case Report

“…This emphasizes the need for evaluating the role of radium-223 earlier in the disease course and in combination with systemic agents. Different trials are currently evaluating the efficacy of radium-223 in breast cancer in combination with paclitaxel (NCT04090398), endocrine treatments (aromatase inhibitors plus everolimus; NCT02258451), and capecitabine (ISRCTN92755158) ( 8 ).…”

Diagnosis and Treatment of Bone Metastases in Breast Cancer: Radiotherapy, Local Approach and Systemic Therapy in a Guide for Clinicians

“…In another study, breast cancer patients with predominant bone disease underwent 223 Ra therapy with metabolic activity reduction of lesions and a good safety profile [ 100 ]. CARBON trial, registered o 2016, is investigating a possible combination of 223 Ra and capecitabine in terms of safety and disease control for metastatic breast cancer patients with bone involvement [ 101 ]. Limitations of radiopharmaceuticals is their myelosuppressive persistent effect and indication to use principally in the palliative setting.…”

Targeted Palliative Radionuclide Therapy for Metastatic Bone Pain

“…Not surprisingly, [ 223 Ra]RaCl is the subject of ongoing trials in other bone dominant metastatic cancers such as breast [ 140 , 141 ] and lung cancers [ 142 ]. In a phase II trial, [ 223 Ra]RaCl has been administered with different hormonal therapy agents [ 141 ].…”

“…The primary end-point was disease control at 9 months, achieved in 49% of patients [ 141 ]. In addition, the study evaluating the efficacy of combined therapy of [ 223 Ra]RaCl in association with hormonal therapy and a chemotherapy drug (capecitabine) is still in progress [ 140 ].…”