Recurrent Breast Carcinoma, Stage IV Breast Cancer
Conditions
Brief summary
This phase II trial studies how well eribulin mesylate works in treating patients with previously treated breast cancer that has spread to other places in the body. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Detailed description
PRIMARY OBJECTIVES: I. Progression free survival (PFS). SECONDARY OBJECTIVES: I. Frequency of alopecia with absence or decrease to \< 50%. II. Incidence of grade 3 and 4 neutropenia of \< 30%. III. Incidence of sensory neuropathy (all grades) to \< 25%. TERTIARY OBJECTIVES: I. Assess the role of circulating endothelial cell precursors (CEPs) and apoptotic circulating endothelial cells (CECs), in predicting early response to treatment. OUTLINE: Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 1 year.
Interventions
DRUGEribulin Mesylate
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent * Prior exposure to taxane in the adjuvant, neoadjuvant or metastatic setting * At least one prior regimen of chemotherapy in the setting of metastatic breast cancer; no upper limit on the number of prior endocrine regimens for metastatic breast cancer, however no more than 6 chemotherapeutic regimens may have been given in the metastatic setting * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Patients must have baseline imaging within 30 days prior to the start of therapy and satisfy one of the following: * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria * At least one non lymph node lesion of \>= 1.0 cm or lymph node \>= 1.5 cm in short axis by computerized tomography (CT) scan (CT scan thickness no greater than 5 mm which is serially measurable according to RECIST 1.1 using either computerized tomography (CT) or magnetic resonance imaging (MRI) * Lesions that have had radiotherapy must show evidence of progressive disease (PD) based on RECIST 1.1 to be deemed a target lesion * Non-measurable disease by RECIST 1.1 criteria (includes bone only disease and lesions \< 10 mm or lymph nodes \< 15 mm in short axis) with rising serum CA15-3 or CA 27.29 or CEA documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration. The second CA 15-3 or CA 27.29 value must have at least a 20% increase over the first and for CA 15-3 or CA27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL * Absolute neutrophil count \>= 1,500/mm\^3 * Hemoglobin \>= 10 g/dL * Platelets \>= 100,000/mm\^3 * Creatinine =\< 1.5 x upper limit of normal (ULN) * Total bilirubin =\< 1.5 x ULN * Alkaline phosphatase =\< 3.0 x ULN; up to 5 x ULN is acceptable if due to bone metastases in the absence of liver metastases * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal, unless due to liver metastases (=\< 5 x ULN) * Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation * Life expectancy of \> 12 weeks
Exclusion criteria
* Prior treatment with eribulin * Plan to administer any other systemic antitumor including endocrine therapy except for following standard of care treatment: * Trastuzumab at standard dosing human epidermal growth factor receptor 2 (HER2) positive tumors * Denosumab or bisphosphonates to treat metastatic bone disease * Plan to administer concurrent radiation therapy now or for progressive symptoms during treatment * Patients with known central nervous system (CNS) metastases must have stable disease off steroids after treatment with surgery or radiation therapy * Second primary malignancy that is clinically detectable or clinically significant at the time of consideration for study enrollment * Patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic and/or moderate (creatinine clearance \[CrCl\] 30-50 mL/min) renal impairment * Radiotherapy within 14 days of study treatment * Major surgery within 21 days of study treatment; minor surgery within 2 weeks of study treatment; placement of vascular access device and biopsies allowed and is not considered major or minor surgery * Treatment with any systemic chemotherapy or investigational agents within 3 weeks of the start of study treatment; endocrine treatment must be stopped prior to initiating study treatment; subjects must have recovered from toxicities of prior therapy * Patients with peripheral neuropathy \> grade 2 regardless of etiology * Significant cardiovascular impairment: congestive heart failure \> class II according to the New York Heart Association (NYHA), unstable angina or myocardial infarction within 6 months of enrollment, or serious cardiac arrhythmia (\> grade 2) * Concomitant severe or uncontrolled medical disease * Significant psychiatric or neurologic disorder which would compromise participation in the study * Pregnant or breast-feeding females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From study enrollment until the earliest date of disease progression or death, assessed up to 1 year | Kaplan-Meier survival curves will be used to describe PFS, overall and stratified by number of prior metastatic treatment regimens. A 95% confidence interval for the median PFS will be calculated using the method of Brookmeyer and Crowley. |
Countries
United States
Participant flow
Pre-assignment details
86 patients signed the study informed consent, but only 68 patients started the Eribulin treatment. Out of those 68 patients only 59 of them were evaluable.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Eribulin Mesylate) Patients receive eribulin mesylate IV over 2-5 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Eribulin Mesylate: Given IV
Laboratory Biomarker Analysis: Correlative studies | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not complete the first cycle | 4 |
| Overall Study | Incorrect Diagnosis | 2 |
| Overall Study | Incorrect Starting Dose | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Eribulin Mesylate) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants |
| Age, Continuous | 52 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 49 Participants |
| Region of Enrollment United States | 59 Participants |
| Sex: Female, Male Female | 59 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 44 / 59 |
| other Total, other adverse events | 23 / 59 |
| serious Total, serious adverse events | 2 / 59 |
Outcome results
Primary
PFS
Kaplan-Meier survival curves will be used to describe PFS, overall and stratified by number of prior metastatic treatment regimens. A 95% confidence interval for the median PFS will be calculated using the method of Brookmeyer and Crowley.
Time frame: From study enrollment until the earliest date of disease progression or death, assessed up to 1 year
Population: Patients with metastatic breast cancer (MBC) whose disease has progressed following at least one prior regimen of chemotherapy in the setting of metastatic breast cancer
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Eribulin Mesylate) | PFS | 3.5 months |
Comparison: Progression free survival (PFS). We hypothesize that metronomic dosing of eribulin will result in a PFS of 4-6 months.95% CI: [2.6, 4.6]