Topic: Cancer
Conditions
Interventions
Patients in the initial safety phase will receive capecitabine plus radium-223. Patients in the randomised extension phase will be randomised to receive either oral capecitabine alone or capecitabine
Sponsors
Sheffield Teaching Hospitals NHS Trust
Eligibility
Sex/Gender
Female
Inclusion criteria
Inclusion criteria: 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| As of 07/03/2016: Initial safety phase 1. Dose limiting toxicities Randomised extension phase 1. Frequency of CTC grade III-IV toxicities with a focus on diarrhoea as the primary dose limiting toxicity 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. Previous primary outcome measures: To evaluate the safety and toxicity of the combination of radium-223 and capecitabine | — |
Secondary
| Measure | Time frame |
|---|---|
| As of 07/03/2016: 1. Safety endpoints 1.1. Adverse events (AEs) and serum biochemistry and haematology abnormalities graded according to the Common Toxicity Criteria for Adverse Events (CTC) version 4.03 1.2. Serious adverse events 1.3. Dose delays and reductions due to toxicity 2. Efficacy endpoints 2.1. Changes from baseline in serum bone turnover markers (B-ALP, uNTX, P1NP, CTX and 1CTP) throughout the study period 2.2. Time to occurrence of 1st symptomatic skeletal event (SSE). This is time from registration / randomisation to 1ST SSE. Patients who do not experience an SSE by the time of final analysis will be censored at the last time known to have not experienced as SSE, study withdrawal, start of new treatment or death 2.3. Time to progression of bone disease based on unequivocal progression of existing bone lesions or appearance of one or more new osteolytic bone lesions. This is time from registration/randomisation to progression in bone. Patients who do not progress in bone by time of final analysis will be censored at the last time known to have not progressed in bone, study withdrawal, start of new treatment or death 2.4. Time to progression of extraskeletal disease. This is time from registration / randomisation to progression in extraskeletal non bony sites. Patients who do not progress outside bone by time of final analysis will be censored at the last time known to have not progressed outside bone, study withdrawal, start of new treatment or death 3. Clinical benefit endpoints 3.1. Pain scores using the Brief Pain Inventory (BPI) 3.2. Quality of life using the EORTC BM-22 bone metastases module Previous secondary outcome measures: To evaluate the effect of radium-223 on other bone turnover markers (P1NP, CTX, 1CTP, B-ALP) | — |
Countries
England, United Kingdom
Contacts
Public ContactAmber Reid
Outcome results
None listed