Eribulin Mesylate in Treating Patients with Locally Advanced or Metastatic Angiosarcoma or Epithelioid Hemangioendothelioma

Status: Active

Description

This pilot phase II trial studies how well eribulin mesylate works in treating patients with angiosarcoma or epithelioid hemangioendothelioma that has spread from where it started to nearby tissue or lymph nodes or 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.

Eligibility Criteria

Inclusion Criteria

  • Metastatic or locally advanced angiosarcoma, treated with at least one prior systemic therapy where no standard of care curable therapy is available OR metastatic or locally advanced malignant and progressive epithelioid hemangioendothelioma (EHE) * A maximum of 5 EHE patients will be accrued on this study
  • Archival tissue confirming the diagnosis must be reviewed by Brigham and Women's Hospital (BWH)/Dana-Farber Cancer Institute (DFCI)/Massachusetts General Hospital (MGH) pathology
  • Progression on at least one prior systemic therapy or progression during an observation phase of no anti-cancer therapy within the prior 3 months; prior taxanes are allowed
  • Participants must have measurable disease by RECIST 1.1, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of greater than 3 months
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine clearance >= 50 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
  • Baseline Fridericia's correction formula (QTcF) < grade 2
  • Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation, and 4 months after completion of eribulin administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of eribulin administration
  • Willingness to undergo serial tumor biopsies before and on treatment
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C), immunotherapy within 3 weeks, targeted therapies (e.g. small molecule inhibitors such as pazopanib) within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; not clinically significant or clinically stable adverse events from prior therapy (e.g. immunotherapy related hypothyroidism or insulin-dependent diabetes stable on medication or tyrosine kinase inhibitor [TKI]-related hypertension or rash etc.) is allowed
  • Participants who are receiving any other investigational agents
  • Participants with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study; any signs (e.g. radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment; participants with leptomeningeal disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to eribulin
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class II), unstable angina pectoris or myocardial infarction within 6 months of enrollment, serious or life-threatening cardiac arrhythmia, subjects with a high probability of long QT syndrome or QTcF prolongation of >= 501 mcsec (grade 2) on at least two separate electrocardiography (ECG) following correction of any electrolyte imbalance or psychiatric illness/social situations that would limit compliance with study requirements
  • Females who are breastfeeding or pregnant at screening or baseline (as documented by a positive beta-human chorionic gonadotropin [beta-hCG] [or human chorionic gonadotropin (hCG)] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-hCG [or hCG]); a separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug
  • Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated

Locations & Contacts

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Contact: Katherine Anne Thornton
Phone: 617-632-6478
Email: katherinea_thornton@dfci.harvard.edu
Dana-Farber Cancer Institute
Status: Active
Contact: Katherine Anne Thornton
Phone: 617-632-6478
Email: katherinea_thornton@dfci.harvard.edu
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Gregory Michael Cote
Phone: 617-726-8748
Email: gcote@partners.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the objective response rate (ORR, partial response [PR]+complete response [CR]) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of angiosarcoma/epithelioid hemangioendothelioma (EHE) patients treated with eribulin mesylate (eribulin).

SECONDARY OBJECTIVES:

I. To further characterize the clinical activity of eribulin in this population by progression-free survival (PFS).

II. To further characterize the clinical activity of eribulin in this population by disease control rate (DCR = ORR + stable disease [SD] at 24 weeks).

III. To further characterize the safety profile of eribulin in this patient population.

EXPLORATORY OBJECTIVES:

I. To determine any correlation between angiosarcoma or sarcoma subtype and response.

II. To determine any correlation between response and genomic characterization of the sarcoma.

III. To determine genomic and expression profile changes, via biopsy samples and/or circulating free deoxyribonucleic acid (DNA) exome sequencing, over time after treatment with eribulin.

OUTLINE:

Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 28 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Gregory Michael Cote

Trial IDs

Primary ID 17-355
Secondary IDs NCI-2018-00169
Clinicaltrials.gov ID NCT03331250