Clinical trial NCT01908101: Eribulin Mesylate in Treating Patients With Previously Treated Metastatic Breast Cancer
Official title: Phase II Trial of Metronomic Eribulin (Halaven) in Pretreated Metastatic Breast Cancer (MBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Breast Carcinoma
Stage IV Breast Cancer
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2013-07-25
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: PFS
timeFrame: From study enrollment until the earliest date of disease progression or death, assessed up to 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Katmai Oncology Group
state: Alaska
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Tucson
country: United States
facility: The University of Arizona Medical Center-University Campus
state: Arizona
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Bend
country: United States
facility: Bend Memorial Clinic
state: Oregon
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital
state: Washington
city: Port Angeles
country: United States
facility: Olympic Medical Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
city: Seattle
country: United States
facility: Group Health Cooperative-Seattle
state: Washington
city: Tacoma
country: United States
facility: MultiCare Tacoma General Hospital
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital and Clinics
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Hannah Linden
role: PRINCIPAL_INVESTIGATOR
References: