Metastatic hormone receptor positive breast cancer (primary or recurrent), defined as ER+ >1% in metastatic biopsy (archival material or study biopsy) and HER2 negative in the last biopsy evaluable for HER2. MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Yervoy (ipilimumab)
Product Name: Yervoy
Pharmaceutical Form: Solution for infusion
Trade Name: Opdivo (nivolumab)
Product Name: Opdivo
Pharmaceutical Form: Solution for infusion
Trade N
Sponsors
Oslo University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Metastatic hormone receptor positive breast cancer (primary or recurrent), defined as ER+ >1% in metastatic biopsy (archival material or study biopsy) or cytology and HER2 negative in the last biopsy or cytology evaluable for HER2. HER2-analysis is to be perfomed according to national criteria. 2. Adequate core or excisional study biopsy of a tumor lesion. Lesions in previously irradiated areas may only be used for the biopsy if the lesion has appeared or progressed after radiation. . No anti-tumor treatment is allowed between the time point for biopsy and study entry. 3. Measurable metastatic disease according to RECIST 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 5. Signed Informed Consent Form 6. Women or men aged = 18 years 7. A minimum of 12 months from adjuvant/neoadjuvant chemotherapy with antracyclins to relapse of disease. 8. A maximum of one previous line with chemotherapy in the metastatic setting 9. Chemotherapy is considered as preferred treatment 10. Previous endocrine and targeted therapy is allowed 11. No use of systemic corticosteroids at study entry 12. Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 13. Female subjects of childbearing potential should agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Malignancies other than breast cancer within 5 years prior to randomization 2. Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization 3. Known CNS disease, except for asymptomatic CNS metastases, provided all of the following criteria in the protocol are met. 4. Uncontrolled pleural effusion, pericardial effusion, or ascites. Patients with indwelling catheters are allowed 5. Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to randomization. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain should be considered for loco-regional therapy if appropriate prior to randomization 6. Ionized calcium > 1.2 x UNL. 7. Pregnant or breastfeeding 8. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease 9. Significant cardiovascular disease. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF < 50% must be on a stable medical regimen that is optimized 10. Severe infection within 21 days prior to randomization, requiring hospitalization 11. Received oral or IV antibiotics within 1 week prior to Cycle 1, Day 1. 12. Major surgical procedure within 21 days prior to randomization or anticipation of the?need for a major surgical procedure during the course of the study other than for diagnosis. 13. A history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 14. Known hypersensitivity to any of the components of the investigational products 15. A history of autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.? Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only are permitted provided that they meet all of the following conditions defined in the protocol. 16. Undergone allogeneic stem cell or solid organ transplantation 17. A history of idiopathic pulmonary fibrosis or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted 18. A positive test for HIV 19. Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. 20. Active tuberculosis 21. Currently receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment 22. Received treatment with immune checkpoint modulators 23. Received treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization 24. Received treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial a. Patients wh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assessment of toxicity of combined treatment with ipilimumab, nivolumab, pegylated liposomal doxorubicin and cyclophosphamide (ipi/nivo/chemo) Assessment of clinical response in ipi/nivo/chemo group compared to chemo only group: Progression-free survival (PFS); compare the PFS rates when 95% of patients in the control croup have PD;Secondary Objective: Assessment of clinical response in ipi/nivo/chemo group compared to chemo only group: Objective tumor response rate (ORR), duration of response (DR), durable tumor response rate (DRR; >6 months), clinical benefit rate (CBR), overall survival (OS) Assessment of toxicity of ipi/nivo (without chemotherapy) in cross-over arm Assessment of ORR, DR, DRR, PFS and OS in cross-over arm receiving ipi/nivo (without chemotherapy) Assessment of PD-L1 expression, mutation load and immune gene expression as biomarkers for clinical response Assessment of patient reported outcomes, as measured by the Chalder Fatigue Questionnaire (FQ), an 11 point Numerical Rating Scale (NRS) for pain intensity and EORTC QLQ-C15-PAL ;Primary end point(s): Assessment of toxicity Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: Compare the PFS rates when 95% of patients in the control croup have PD | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Objective tumor response rate (ORR), duration of response (DR), durable tumor response rate (DRR; >6 months), overall survival (OS);Timepoint(s) of evaluation of this end point: Approximately 3 years | — |
Countries
Belgium, France, Norway
Contacts
Public ContactNational Coordinating Investigator
Oslo University Hospital
Outcome results
None listed