Clinical trial NCT04061863: Nivolumab and Eribulin in HER2 Negative Metastatic Breast Cancer
Official title: A Phase IB/II, Single Arm, Multi-center Study of Nivolumab in Combination With Eribulin in HER2 Negative Metastatic Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
Keywords: breast cancer
eribulin
nivolumab
immunotherapy
immune checkpoint inhibitor
metastatic breast cancer
PD-1
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Seoul National University Bundang Hospital
name: Korean Cancer Study Group (KCSG)
name: Eisai Korea Inc.
name: Ono pharmaceutical Korea
First posted: 2019-08-20
Enrollment: 90
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: ER+/HER2- BC cohort: 45 pts ER-/HER2- (Triple negative) BC cohort: 45 pts
Primary purpose: TREATMENT

Brief summary: Cancer therapeutics such as chemotherapy may modulate tumor/immune-system interactions in favor of the immune system. Chemotherapy can result in tumor cell death with a resultant increase in tumor antigen delivery to antigen-presenting cells. Therefore, combining immunotherapy (Nivolumab) with chemotherapy (Eribulin) is a promising anti-cancer strategy.


Eligibility criteria: Inclusion Criteria:

* Provision of informed consent prior to any study specific procedures
* Age 20 years or older
* ECOG performance status(PS) 0 or 1
* Histologically confirmed stage IV or recurrent breast cancer
* 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)
* 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
* 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 will not be counted as a prior line of treatment
* Measurable disease according to RECIST v 1.1.

Exclusion Criteria:

* Previous treatment with eribulin mesylate or any anti-PD-1, PD-L1, or PD-L2
* Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive 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.
* 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
* Known history of human immunodeficiency virus (HIV) positive
* Known active hepatitis B or hepatitis C (eg, HCV RNA detected)
* 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
* History of significant cardiovascular disease
* Hypersensitivity to the active substance or any other excipients of the eribulin mesylate drug product, or to nivolumab
* Scheduled for major surgery during the study
* 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
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Has a history of interstitial lung disease
* 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.

Primary outcomes:
measure: 6 months progression-free survival (PFS) rate
timeFrame: 6 months
Secondary outcomes:
measure: Objective response rate by RECIST criteria v 1.1
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years (upto 5 years)
measure: Incidence Rate of each Toxicity by CTCAE 4.0
timeFrame: 2 years (upto 5 years)
measure: Clinical benefit rate by RECIST criteria v 1.1 (and iRECIST)
timeFrame: 2 years
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
Study officials:
affiliation: Seoul National University Bundang Hospital
name: JEEHYUN KIM, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: