Rob Coleman1, Janet Brown1, Emma Rathbone2, Louise Flanagan3, Amber Reid3, Jessica Kendall4, Sacha Howell5, Chris Twelves6,7, Carlo Palmieri8,9, Anjana Anand10, Iain MacPherson11, Sarah Brown3. 1. The University of Sheffield, Sheffield, UK. 2. Calderdale and Huddersfield NHS Foundation Trust, Huddersfield, UK. 3. Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. 4. Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK. J.E.Kendall@leeds.ac.uk. 5. The Christie NHS Foundation Trust, Manchester, UK. 6. St James's University Hospital, Leeds, UK. 7. Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds, UK. 8. Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK. 9. University of Liverpool, Liverpool, UK. 10. Nottingham University Hospitals NHS Trust, Nottingham, UK. 11. Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
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. TRIAL REGISTRATION: ISRCTN, ISRCTN92755158, Registered on 17 February 2016.
RCT Entities:
BACKGROUND: A substantial proportion of breast cancerpatients 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.
Entities:
Keywords:
Bone metastases; Bone turnover markers; Breast cancer; Capecitabine; Radium-223
Authors: Matthew Winter; Rob Coleman; Jessica Kendall; Carlo Palmieri; Chris Twelves; Sacha Howell; Iain MacPherson; Caroline Wilson; Kash Purohit; Jacqui Gath; Christine Taylor; Richard Eastell; Geraldine Murden; Sarah R Brown; Emma Rathbone; Janet Brown Journal: J Bone Oncol Date: 2022-06-24 Impact factor: 4.491