Capecitabine oral chemotherapy with radium-223 in breast cancer patients with bone metastases (CARBON)
- Conditions
- Topic: CancerSubtopic: Breast CancerDisease: Bone, BreastCancer
- Registration Number
- ISRCTN92755158
- Lead Sponsor
- Sheffield Teaching Hospitals NHS Trust
- Brief Summary
2020 Protocol article in https://www.ncbi.nlm.nih.gov/pubmed/31941523 protocol (added 17/01/2020) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35800293/ (added 06/03/2024)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Female
- Target Recruitment
- 34
Current inclusion criteria, as of 19/03/2018:
1. Female patients with histological evidence of primary breast cancer
2. Bone metastases (with or without soft tissue, lymph node or visceral metastases; brain metastases allowed if stable and untreated for = 8 weeks)
3. = 2 bone lesions confirmed on imaging (plain radiographs, CT or MRI)
4. Systemic chemotherapy with capecitabine is felt to be appropriate by the treating physician due to recent progression of metastatic disease
5. Received = 2 lines of chemotherapy in the metastatic setting. Prior cytotoxic therapy must have been completed = 28 days prior to initiation of study treatment
6. Patient has been on bone targeted therapy (bisphosphonate or denosumab) for at least 6 weeks prior to start of study treatment and no change to bone targeted therapy is expected during the treatment phase of the study.
7. ECOG performance status 0-2
8. Life expectancy = 6 months
9. Laboratory requirements:
9.1. WBC =3.0 x10 9 /l 3000/mm3
9.2. ANC =1.5 x10 9 /l1500/mm3
9.3. Platelet count =100x109/l
9.4. Haemoglobin =10.0g/dL
9.5. Total bilirubin level =1.5 times ULN in treating institution
9.6. AST and ALT = 3 times ULN in treating institution
9.7. Calculated creatinine clearance or estimated GFR > 50mls/min (Cockcroft and Gault or Wright formula may be used according to local practice)
10. Patient must be willing and able to comply with the protocol, including follow-up visits and investigations and use effective contraception if relevant throughout the study and for at least 6 months after treatment completion
11. Must be fully informed about the study and has signed the informed consent form
12. Age at least 18 years
Previous inclusion criteria:
1. Female patients with histological evidence of primary breast cancer
2. Bone metastases (with or without soft tissue, lymph node or visceral metastases; brain metastases allowed if stable and untreated for = 8 weeks)
3. = 2 bone lesions confirmed on imaging (plain radiographs, CT or MRI)
4. Systemic chemotherapy with capecitabine is felt to be appropriate by the treating physician due to recent progression of metastatic disease
5. Received = 2 lines of chemotherapy in the metastatic setting. Prior cytotoxic therapy must have been completed = 28 days prior to initiation of study treatment
6. Patient has been on bone targeted therapy (bisphosphonate or denosumab) for at least 3 months prior to start of study treatment and no change to bone targeted therapy is expected during the treatment phase of the study
7. ECOG performance status 0-2
8. Life expectancy = 6 months
9. Laboratory requirements:
9.1. WBC =3.0 x10 9 /l 3000/mm3
9.2. ANC =1.5 x10 9 /l1500/mm3
9.3. Platelet count =100x109/l
9.4. Haemoglobin =10.0g/dL
9.5. Total bilirubin level =1.5 times ULN in treating institution
9.6. AST and ALT = 3 times ULN in treating institution
9.7. Calculated creatinine clearance or estimated GFR > 50mls/min (Cockcroft and Gault or Wright formula may be used according to local practice)
10. Patient must be willing and able to comply with the protocol, including follow-up visits and investigations and use effective contraception if relevant throughout the study and for at least 6 months after treatment completion
11. Must be fully informed about the study and has signed the informed consent form
12. Age at least 18 years
1. Received an investigational drug within 4 weeks prior to the first study treatment
2. Received external beam radiotherapy within 4 weeks prior to the first study treatment
3. Presence of imminent or established spinal cord compression based on clinical findings and/or MRI
4. Presence of other currently active (diagnosis within the last 5 years) malignancy (except treated non-melanoma skin cancer (basal or squamous), carcinoma in situ of cervix and superficial bladder cancers).
5. Patients who have had severe and unexpected reactions to fluoropyrimidine therapy or have been diagnosed with dihydropyrimidine dehydrogenase deficiency
6. Received a blood transfusion or Use of erythropoietin within 4 weeks of study treatment
7. Pregnant or breast-feeding women.
8. Treatment with sorivudine or its chemically related analogues, such as brivudine
9. Treatment with phenytoin or warfarin
10. Patients with any other serious illness or medical condition, such as, but not limited to:
10.1. Any uncontrolled infection
10.2. Clinical heart failure (NYHA Heart Failure Class III or IV)
10.3. Active Crohn’s disease or ulcerative colitis
10.4. Bone marrow myelodysplasia
10.5. Uncontrolled coronary artery disease
10.6. Active peptic ulcers
10.7. Malabsorption
11. Any exclusions as per the Xofigo or Capecitabine SmPC
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method As of 07/03/2016:<br>Initial safety phase<br>1. Dose limiting toxicities<br><br>Randomised extension phase<br>1. Frequency of CTC grade III-IV toxicities with a focus on diarrhoea as the primary dose limiting toxicity<br>2. Decrease in uNTX from baseline to end of cycle 5 (approximately 15 weeks post trial entry). For patients who progress prior to the end of cycle 5, the decrease in uNTX from baseline to their end of study treatment visit will be used.<br><br>Previous primary outcome measures:<br>To evaluate the safety and toxicity of the combination of radium-223 and capecitabine
- Secondary Outcome Measures
Name Time Method