Eribulin With or Without Trastuzumab-biosimilar in Patients With HER2-overexpressed Recurrent or Stage IV Breast Cancer
Randomized, Open Label, Multi-Center, Phase II Trial of Eribulin With or Without SB3 (Trastuzumab-biosimilar) in Patients With HER2-overexpressed Recurrent or Stage IV Breast Cancer Who Have Received at Least 2 Prior HER2-directed Regimens
Seoul National University Hospital
180 participants
Feb 18, 2020
INTERVENTIONAL
Conditions
Summary
Optimal salvage treatment for HER2-positive breast cancer after trastuzumab and T-DM1 failure still remains to be established. We would like to investigate the efficacy and safety of combination chemotherapy of eribulin and trastuzumab as salvage treatment for HER2-Positive breast cancer after exposure to trastuzumab and T-DM1
Eligibility
Inclusion Criteria18
- Adults ≥18 years old.
- Pathologically documented breast cancer that:
- is unresectable or metastatic
- has confirmed HER2 positive expression (immunohistochemistry or FISH) as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines evaluated at a central laboratory
- was previously treated with trastuzumab, T-DM1 or T-Dxd, and taxane (whether in recurrent/metastatic setting or neoadjuvant/adjuvant setting).
- Less than 4 prior lines of chemotherapy or HER2 targeted therapies for treatment in metastatic disease (\<4 treatment regimens for recurrent/metastatic disease excluding adjuvant treatments)
- Documented radiologic progression (during or after most recent treatment or within 6 months after completing adjuvant therapy).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1
- Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 4.5 months after the last dose of study treatment.
- Adequate hematopoietic, renal and hepatic functions.
- Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet≥100,000/mm3, hemoglobin≥10g/mm3
- Adequate hepatic function: total bilirubin ≤2.0mg/dL, AST/ALT ≤2 x UNL, alkaline phosphatase ≤2.5 x UNL, in case with bone metastases alkaline phosphatase ≤5 x UNL
- Adequate renal function: Serum creatinine ≤1.5mg/dL
- a left ventricular ejection fraction of 50% or more (determined by echocardiography or multiple-gated acquisition \[MUGA(Multigated Blood Pool Scan)\] scanning)
- CNS(central nervous system) metastasis is permitted if asymptomatic or controlled with minimal steroid requirement and is documented to be non-progressing at study entry.
- Negative result for urine or serum pregnancy tests within the screening period in premenopausal patients
- Ability to understand and comply with protocol during study period
- Patients should sign a written informed consent before study entry
Exclusion Criteria14
- Prior treatment with eribulin
- Uncontrolled or significant cardiovascular disease
- History of documented congestive heart failure (CHF) or systolic dysfunction (LVEF \<50%)
- High-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade Atrioventricular-block, supraventricular arrhythmias, prolonged QTc(corrected QT interval) which are not adequately rate-controlled)
- Angina pectoris requiring antianginal medication
- Clinically significant valvular heart disease
- Evidence of transmural infarction on ECG
- Poorly controlled hypertension (e.g. systolic \>180mm Hg or diastolic \>100mm Hg)
- Pregnant or lactating women or women of childbearing potential, including women whose last menstrual period was ,12 months ago (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during the study treatment period.
- Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer and thyroid cancer. For other types of cancer, patients could be included if there is no evidence of disease for more than 2 years.
- Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative colitis)
- Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
- Concurrent disease or serious medical disorder, for example, active or uncontrolled infection, interstitial lung disease (ILD) or any psychiatric condition prohibiting understanding or rendering of informed consent.
- Patients who have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients.
Interventions
* Patients will receive eribulin mesylate 1.4 mg/m2 administered I.V. with infusion over 2 to 5 minutes on days 1 and 8 of each 21-day cycle and SB3 8 mg/kg I.V. over 90 minutes on day 1 of cycle 1 . Thereafter, SB3 6 mg/kg will be infused over 30 minutes on day 1 of each subsequent 21-day cycle until progression or unacceptable toxicity. * Dose reductions for eribulin, but not for SB3, is permitted. * Two dose reductions (1.1, 0.7 mg/m2) are allowed for eribulin before consideration of study treatment discontinuation. Eribulin could be continued as monotherapy if trastuzumab-similar was discontinued, and vice-versa.
* Patients will receive eribulin mesylate 1.4 mg/m2 administered I.V. with infusion over 2 to 5 minutes on days 1 and 8 of each 21-day cycle until progression or unacceptable toxicity. * Two dose reductions (1.1, 0.7 mg/m2) are allowed before consideration of study treatment discontinuation.
Locations(1)
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NCT05530057