Eribulin in Angiosarcoma and Epithelioid Hemangioendothelioma (EHE)

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational drug to learn whether the drug works in treating a
specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Eribulin for your specific
disease but it has been approved for other uses.

In this research study, the investigators are studying how safe and effective eribulin is in
participants with Angiosarcoma or EHE.

Eribulin was created to mimic the structure of a chemical that is released from a sea sponge.
The investigators believe that this drug has anti-cancer effects on tumors by blocking
proteins called microtubules, among other functions. It may work by preventing the cancer
cells from dividing and eventually cause the tumor cells to die similar to other drugs that
target microtubules

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 BWH/DFCI/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 CT scan, MRI, or calipers by clinical
exam.

- Age > 18 years.

- ECOG performance status ≤2

- Life expectancy of greater than 3 months

- Participants must have normal organ and marrow function as defined below:

- leukocytes ≥3,000/mcL

- absolute neutrophil count ≥1,000/mcL

- platelets ≥100,000/mcL

- total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

- creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels
above institutional normal.

- Baseline QTcF < grade 2

- The effects of Eribulin on the developing human fetus are unknown. For this reason and
because of the risk of teratogenicity, 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 TKI-related hypertension or rash
etc.) is allowed.

- Participants who are receiving any other investigational agents.

- Participants with known brain metastases and/or 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 (NYHA Class II), unstable angina
pectoris or myocardial infarction within 6 months of enrolment, 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 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 [ß-hCG] (or human chorionic gonadotropin
[hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-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.

- HIV-positive participants on combination antiretroviral therapy are ineligible because
of the potential for pharmacokinetic interactions with Eribulin. In addition, these
participants are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in participants
receiving combination antiretroviral therapy when indicated