A Multi-center Study to test efficacy and safety of Nivolumab in Combination with Eribulin in previously treated HER2 (Human Epidermal growth factor Receptor-2) negative Metastatic Breast Cancer patients
- Conditions
- Neoplasms
- Registration Number
- KCT0003826
- Lead Sponsor
- Seoul National University Bundang Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- Female
- Target Recruitment
- 108
1.Provision of informed consent prior to any study specific procedures
2.Age 20 years or older
3.ECOG PS 0 or 1
4.Histologically confirmed breast cancer
5.Stage IV or recurrent breast cancer that cannot undergo curative surgery
6.HER2 negative disease: not eligible for anti-HER2 therapy
HER2 negative [IHC 0, 1+ or IHC 2+ with corresponding ISH non-amplified or ratio less than 2.0 or ISH non-amplified ratio less than 2.0] as per ASCO-CAP HER2 guideline recommendations 2013 (ASCO-CAP)
7.Patients previously treated with anthracycline and/or taxane unless contraindicated
; Patients who received anthracycline and/or taxane based chemotherapy in either the neoadjuvant, adjuvant or metastatic setting and experienced disease progression on or after taxane-based chemotherapy in the metastatic setting
8.No more than 3 prior lines of cytotoxic chemotherapy for metastatic disease
; patients who experienced disease recurrence within 1 year after completion of (neo)adjuvant anthracycline and taxane-based chemotherapy will be counted as 1 prior line of treatment.
; hormonal therapy (including CDK4/6 inhibitor, MTOR inhibitor) will not be counted as a prior line of treatment
9.Evaluable disease according to RECIST v 1.1.
10.Expected survival > 12 weeks
11.Patients must have adequate organ and marrow function as defined below:
Absolute neutrophil count (ANC) = 1.5 x 109/L, Absolute lymphocyte count 0.5 x 109/L
Hemoglobin = 9.0 g/Dl (transfusion allowed)
Platelet = 100 x 109/L,
AST and/or ALT = 3 × upper limit of normal (ULN), ALP =2.5 x ULN
[subjects with AST and/or ALT = 5 X ULN can be enrolled if they have liver metastases]
Total bilirubin: = 1.5 × ULN; Patients with Gilbert syndrome with total bilirubin = 3 × ULN can be eligible)
Serum creatinine clearance) > 50mL/min (by Cockcroft-Gault formula, MDRD, CKD-EPI formula or 24hr urine collection)
12.Complications of previously received radiotherapy or chemotherapy are fully restored to baseline level or to grade 1 according to NCI-CTCAE version 4.03.
13.Women of child-bearing potential must use effective contraceptive methods throughout the study treatment from the screening.
14.Formalin-fixed, paraffin-embedded tumor blocks or at least 15 unstained slides are secured.
1)Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2
2)Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppresive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment.
3)Known central nervous system (CNS) disease, except for those subjects with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period
4)Known leptomeningeal metastasis
5)Known history of human immunodeficiency virus (HIV) positive
6)Known active hepatitis B or hepatitis C (eg, HCV RNA detected)
7)Any other malignancy that required treatment or has shown evidence of recurrence (except for nonmelanoma skin cancer, or histologically confirmed complete excision of carcinoma in situ) during the 3 years prior to enrollment in this study
8)History of significant cardiovascular disease, including myocardial infarction (within the past 6 months), congestive heart failiure, and ventricular arrhythmias requiring treatment
9)Hypersensitivity to the active substance or any other excipients of the eribulin mesylate drug product, or to nivolumab
10)Scheduled for major surgery during the study
11)Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be allowed
12)Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
13)Has a history of interstitial lung disease.
14)Has received a live-virus vaccination within 30 days of planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted.
15)History of allogeneic bone marrow transplantation or organ transplantation
16)Any anticancer treatment including endocrine therapy, radiotherapy, cytotoxic chemotherapy, radiotherapy, and/or biologic agents within 14 days of the first dose of study treatment.
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To define a recommended phase 2 dose (RP2D) (Phase 1 part);the progression-free survival (PFS) rate at 6 months for nivolumab and eribulin combination treatment in ER+/HER2- subjects and ER-/HER2- subjects
- Secondary Outcome Measures
Name Time Method Objective response rate by RECIST criteria v 1.1 (and iRECIST);disease control rate at 24 weeks;progression-free survival;overall survival;safety profile;Exploratory analysis