CARBON
Research type
Research Study
Full title
A randomised phase IB/IIA study of CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases (CARBON)
IRAS ID
187500
Contact name
Janet Brown
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS Foundation Trust
Eudract number
2015-003979-29
Duration of Study in the UK
2 years, 5 months, 31 days
Research summary
Summary of Research
This study will investigate the safety and side effects of radium-223 plus capecitabine treatment in breast cancer patients whose disease has spread to the bone. Such patients are at risk of complications including pain, fracture, spinal cord compression, high levels of calcium in the blood and may require extra treatments (surgery, radiotherapy). Radium-223 delivers radiotherapy directly to areas of bone where the cancer exists with minimal harm to other body parts. For this reason it is thought to be an effective treatment for bones without causing significant side effects.
There are two parts to this study, an initial safety phase and a randomised extension phase.
In the initial safety phase, patients in two cohorts of three patients will receive capecitabine and radium-223. A further two cohorts of three patients at a lower capecitabine dose may also be recruited if protocol specified unacceptable side effects are seen. If after these cohorts the side effects are within the acceptable limits, the trial will move onto a randomised extension phase with patients randomised on 1:2 basis to either capecitabine alone or capecitabine plus radium-223.
Patients are seen for assessment, bloods and capecitabine prescribing every three weeks. Radium-223 is given from cycle 2 every 6 weeks (for applicable patients). Radium-223 injections are in the middle of the week off the capecitabine tablets to minimise any interaction between the treatments. Patients can receive up to 12 cycles of treatment and are scanned after 4 and 8 cycles and at the end of treatment. Patients will complete a pain and QOL assessment before the first capecitabine and first radium-223 treatment (if applicable) and then every 6 weeks thereafter.
Three hospitals will recruit up to 48 patients. Recruitment will last for 18 months and follow up will continue until 12 months after the last patient is recruited.
Summary of Results
A randomised phase IB/IIA study of CApecitabine plus Radium-223 (Xofigo™) in breast cancer patients with BONe metastases (CARBON)
Where and when did the study take place?
Participants were recruited at 5 NHS hospitals across England and Scotland. The first site was opened on 28/09/2016, and the trial ran until the last piece of data was collected on 02/08/2021.Who carried out the research?
The trial was sponsored by the Sheffield Teaching Hospitals NHS Trust. The trial was funded and the study drug provided free of charge by Bayer Plc. The trial was supported by Yorkshire Cancer Research (YCR). Day-to-day trial management was carried out by the Leeds Clinical Trials Research Unit (CTRU) at the University of Leeds.Public involvement
2 Patient Public Involvement (PPI) representatives reviewed the Patient Information Sheets before the trial opened. Additionally, these 2 PPI representatives sat on the Safety Review Committee and Trial Management Group for the duration of the trial. This means that they were involved in key decisions on how the trial was run on an ongoing basis.Why was the research needed?
The study was for people who had breast cancer that had spread to their bones. Despite some advances in treatments in this area, there is still an unmet need for further treatment options for these people.Study design
The first six people who took part received radium-223 with capecitabine and they were closely monitored to check that this combination of treatments was safe. The next groups of people either received radium-223 with capecitabine, or capecitabine alone. These groups were compared to check whether the combination was safe, and to give an early indication of whether this combination was effective at treating the cancer.Results
The research team found that the combination of radium-223 with capecitabine was safe in patients with breast cancer that has spread to the bones. However, there was no indication that radium-223 with capecitabine was any more effective at treating the cancer than capecitabine alone.
A total of 34 people joined the trial: 6 in the first group who received the radium-223 with capecitabine, and a further 28 who received either radium-223 with capecitabine, or capecitabine alone.
In total:
• 23 people received radium-223 with capecitabine
• 11 people received capecitabine on its own.
Side effects
In the first group of 6 people who received radium-223 with capecitabine to test its safety, no people had a side effect that was serious enough to suggest the dose they had was a bit high. This indicated that the capecitabine dose given with radium-223 was safe and could be used in the next group of people within the trial.
9 people in each group received all 12 cycles of trial treatment.
In the radium-223 with capecitabine group, 8 out of 23 people experienced a total of 11 serious side effects. In the capecitabine alone group, 2 out of 11 people experienced 7 serious side effects. Most of the serious side effects were related to the disease or to infection.
Some of the most commonly reported side effects were diarrhoea, fatigue and nausea, although these were low grade.How well treatment worked
The team looked at the changes in some biomarkers of bone disease, which were similar for both treatment groups.Details of any further research planned?
Leeds Clinical Trials Research Unit (CTRU) are working on another trial for people with breast cancer that has spread to their bones. This is currently in the planning stage.REC name
London - Fulham Research Ethics Committee
REC reference
16/LO/0052
Date of REC Opinion
3 Feb 2016
REC opinion
Further Information Favourable Opinion