EPTUNE: Determining the safety and assessing the effectiveness of combining avelumab and radium-223 in patients with breast cancer which has spread to the bones
- Conditions
- Breast cancerCancerMalignant neoplasm of breast
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Female
- Target Recruitment
- 33
1. Female patients > = 18 years, with histological evidence of ER+ve, HER2-ve primary breast cancer
2. Radiological evidence of bone metastasis (with or without metastasis at other sites) to include plain radiograph, bone scan, CT or MRI and assessed according to RECIST v1.1, with at least 2 bone metastatic lesions on screening investigations performed at least 6 weeks prior to confirmation of eligibility
3. Measurable disease by RECIST 1.1 (including bone scans – see above)
4. 2-5 prior chemotherapy treatments for advanced disease, including an anthracycline and a taxane, unless contraindicated or patient has declined previous treatment or alternative treatment.
5. ECOG Performance Status 0, 1 or 2.
6. Life expectancy > 6 months
7. Adequate haematological, renal and hepatic function and bone marrow function. Laboratory requirements within 14 days prior to confirmation of eligibility and start of trial treatment as follows;
7.1. Neutrophil count > = 1.5 x10^9/L
7.2. Platelet count > = 100 x10^9/L
7.3. Haemoglobin > = 9.0 g/dL
7.4. Total bilirubin level < = 1.5 xULN in treating institution (or < = 3.0 xULN for patients with Gilbert’s syndrome)
7.5. AST or ALT < = 3 xULN in treating institution
7.6. Calculated creatinine clearance or estimated GFR > 40mls/min (Cockcroft and Gault or Wright formula may be used according to local practice)
8. Patient on bone targeted therapy (e.g. bisphosphonates or denosumab) for > 6 weeks before confirmation of eligibility and starting treatment. No change to bone targeted therapy anticipated during study
9. Able to provide an archival primary tumour biopsy for assay of PD-1 expression (Please note that for Phase IIa participants only, provision of a biopsy from a metastatic lesion if already available, or optional provision of a new metastatic biopsy)
10. Patient must be fully informed about the study and has signed the informed consent form.
11. Patient must be willing and able to comply with the protocol, have mental capacity and (if relevant) use effective contraception throughout treatment and for 6 months after treatment completion.
1. 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).
2. External beam radiotherapy within 4 weeks of confirmation of eligibility and starting treatment.
3. Past medical history of autoimmune disorders or organ transplant including but not limited to myasthenia gravis,myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, poorly controlled type 1 diabetes, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
4. Previous treatment with immune checkpoint inhibitors
5. Active hepatitis B or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. Testing must be performed within 12 months prior to confirmation of eligibility.
6. HIV positive tested within 12 months prior to confirmation of eligibility.
7. Active tuberculosis based on clinical findings.
8. Receipt of an active live vaccine within 4 weeks of confirmation of eligibility and starting treatment.
9. Treatment with systemic immune stimulants or suppressors (including systemic steroids) within 2 weeks of confirmation of eligibility and starting treatment.
10. Requirement for ongoing steroids in the context of active/symptomatic brain/leptomeningeal metastases.
11. Presence of imminent or established spinal cord compression based on clinical findings and/or MRI
12. Known history of clinically significant cardiac disease as documented in the medical records
13. Positive pregnancy test at eligibility assessment for women of childbearing potential or breast-feeding women
14. Known hypersensitivity to any of the excipients of avelumab or radium-223 as documented in the medical records
15. Inability to tolerate antihistamine or antipyretic (e.g. paracetamol) as documented in the medical records
16. Coagulation dysfunction that is deemed by the investigator to be likely to interfere with trial treatment as identified by clotting panel (APTT and INR) within 12 months prior to confirmation of eligibility.
17. Thyroid dysfunction that is deemed by the investigator to be likely to interfere with trial treatment as identified by TSH, free T3 and free T4 within 6 months prior to confirmation of eligibility. Patients with a history of autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
18. Erythropoietin treatment within the 4 weeks prior to confirmation of eligibility and start of treatment
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase Ib initial safety phase:<br>The number of dose-limiting toxicities (DLTs) observed during the DLT period. This will confirm the safety of radium-223 in combination with avelumab<br><br>Randomised expansion phase:<br>Objective response rate (ORR), calculated as the proportion of participants achieving at least a partial response (according to RECIST 1.1 (to include bone response)) within 24 weeks of cycle 1 day 1
- Secondary Outcome Measures
Name Time Method