Nivolumab and Eribulin in HER2 Negative Metastatic Breast Cancer (KORNELIA)
Primary Purpose
Metastatic Breast Cancer
Status
Unknown status
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring breast cancer, eribulin, nivolumab, immunotherapy, immune checkpoint inhibitor, metastatic breast cancer, PD-1
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.
Sites / Locations
- Seoul National University Bundang Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ER+/HER2- breast cancer
ER-/HER2- breast cancer
Arm Description
will be treated with a combination of eribulin and nivolumab
will be treated with a combination of eribulin and nivolumab
Outcomes
Primary Outcome Measures
6 months progression-free survival (PFS) rate
Secondary Outcome Measures
Objective response rate by RECIST criteria v 1.1
Overall survival (OS)
Incidence Rate of each Toxicity by CTCAE 4.0
Clinical benefit rate by RECIST criteria v 1.1 (and iRECIST)
Full Information
NCT ID
NCT04061863
First Posted
August 13, 2019
Last Updated
September 5, 2021
Sponsor
Seoul National University Hospital
Collaborators
Seoul National University Bundang Hospital, Korean Cancer Study Group (KCSG), Eisai Korea Inc., Ono pharmaceutical Korea
1. Study Identification
Unique Protocol Identification Number
NCT04061863
Brief Title
Nivolumab and Eribulin in HER2 Negative Metastatic Breast Cancer
Acronym
KORNELIA
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
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
August 1, 2019 (Actual)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seoul National University Hospital
Collaborators
Seoul National University Bundang Hospital, Korean Cancer Study Group (KCSG), Eisai Korea Inc., Ono pharmaceutical Korea
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
breast cancer, eribulin, nivolumab, immunotherapy, immune checkpoint inhibitor, metastatic breast cancer, PD-1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
ER+/HER2- BC cohort: 45 pts ER-/HER2- (Triple negative) BC cohort: 45 pts
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ER+/HER2- breast cancer
Arm Type
Experimental
Arm Description
will be treated with a combination of eribulin and nivolumab
Arm Title
ER-/HER2- breast cancer
Arm Type
Experimental
Arm Description
will be treated with a combination of eribulin and nivolumab
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
Nivolumab 360mg on D1 every 3 weeks Eribulin 1.4mg/m2 on D1, 8 every 3 weeks
Primary Outcome Measure Information:
Title
6 months progression-free survival (PFS) rate
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Objective response rate by RECIST criteria v 1.1
Time Frame
2 years
Title
Overall survival (OS)
Time Frame
2 years (upto 5 years)
Title
Incidence Rate of each Toxicity by CTCAE 4.0
Time Frame
2 years (upto 5 years)
Title
Clinical benefit rate by RECIST criteria v 1.1 (and iRECIST)
Time Frame
2 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
JEEHYUN KIM, MD,PhD
Organizational Affiliation
Seoul National University Bundang Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Bundang Hospital
City
Seongnam
ZIP/Postal Code
13620
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.kcsg.org/en/index.do
Description
Korea Cancer Study Group
URL
https://www.snubh.org/index.do
Description
Seoul National University Bundang Hospital
Learn more about this trial
Nivolumab and Eribulin in HER2 Negative Metastatic Breast Cancer
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