A Pilot Study of Oraxol in Subjects With Cutaneous Angiosarcoma

Oraxol will be administered once daily for 3 consecutive days every week during the Treatment
Period from Weeks 1 through 25.

Subjects who do not have documented disease progression by the end of the Treatment Period
will be eligible to receive therapy in the Treatment Extension Period; Oraxol may be
administered from Week 26 onwards.

Inclusion Criteria:

- Age of 18 years or older

- Histologically-confirmed cutaneous angiosarcoma that is not amenable to curative
intent surgery (eg, locally advanced disease and disease for which surgical resection
would carry an unacceptable risk of recurrence or morbidity to the subject) Subjects
who have not received taxanes for the treatment of angiosarcoma

- Measurable disease per RECIST v.1.1

- Adequate organ function as defined by the following criteria:

- Adequate renal function as evidenced by serum creatinine ≤1.5 x upper limit of
normal (ULN) or calculated creatinine clearance ≥50 mL/min per the Cockcroft and
Gault formula

- Adequate bone marrow function as evidenced by:

- absolute neutrophil count (ANC) ≥1.5 × 109/L

- hemoglobin ≥9.0 g/dL (<9.0 g/dL is acceptable if it is corrected by
transfusion), and

- platelet count ≥100 × 109/L

- Adequate liver function as evidenced by total bilirubin within normal limits,
alanine aminotransferase (ALT) ≤3×ULN, and aspartate aminotransferase (AST)
≤3×ULN, gamma-glutamyl transferase (GGT) ≤10×ULN, and alkaline phosphatase ≤3×ULN

- Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis)
OR agree to use a condom with spermicide and to not donate sperm during the study and
for at least 30 days following last dose of Oraxol

- Woman of non-child bearing potential due to surgical sterilization (at least 6 weeks
following surgical bilateral oophorectomy with or without hysterectomy or tubal
ligation) confirmed by medical history or menopause (ie, no menstrual bleeding for
more than 12 months in a women aged ≥45 years), OR woman of child-bearing potential
who test negative for pregnancy at time of enrollment based on serum pregnancy test
and agree to use at least 2 acceptable methods of birth control, 1 of which must be
highly effective, during the study and for at least 30 days after stopping Oraxol

- Life expectancy of at least 3 months, in the opinion of the Investigator

Exclusion Criteria:

- Subjects with metastases outside of local lymph node involvement

- Concurrent treatment or participation on other therapeutic clinical trial for
angiosarcoma.

- Women who are pregnant or breastfeeding

- Receipt of systemic cytotoxic therapy, including investigational agents, within 14
days or 5 half-lives of the first study dosing day, whichever is longer

- Major surgery or trauma within 28 days prior to first dose of investigational product.

- Subjects who have received wide-field radiotherapy to the pelvis ≤3 months (defined as
>50% of volume of pelvic bones or equivalent) or limited-field radiation for
palliation ≤3 months prior to treatment administration. Angiosarcoma lesions in the
radiation field are not evaluable unless they have developed progressive disease
following radiation.

- History of brain involvement with cancer, spinal cord compression, or carcinomatous
meningitis, or new evidence of brain or leptomeningeal disease.

- Angina, myocardial infarction, symptomatic congestive heart failure, cerebrovascular
accident, transient ischemic attack, arterial embolism, pulmonary embolism,
percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft
(CABG) within 3 months prior to treatment administration

- Active bleeding or bleeding diathesis actively requiring transfusions; Note: subjects
with cutaneous ulcers from angiosarcoma or who have skin lesions with bleeding are
allowed to participate.

- Thrombolytic use (except to maintain IV catheters) within 10 days prior to treatment
administration

- Presence of a malabsorption syndrome or major resection of the stomach or small bowel
that could affect the absorption of Oraxol

- Known active viral or nonviral hepatitis or cirrhosis

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
related illness

- Active infection that requires systemic treatment

- Concurrent use of a strong cytochrome P450 (CYP) 3A4 inducer (eg, rifampin or St.
John's Wort) or a strong CYP3A4 inhibitor (eg, ketoconazole) within 14 days prior to
treatment administration

- Concurrent use of a strong CYP2C8 inhibitor (eg, gemfibrozil) or inducer (eg,
rifampin) within 14 days prior to treatment administration

- Concurrent use of an oral medication with a narrow therapeutic index known to be a
P-glycoprotein (P-gp) substrate within 24 hours prior to treatment administration

- Concurrent use of a medication known to be a strong P-gp inhibitor or inducer within
14 days prior to treatment administration

- History of hypersensitivity to paclitaxel, not attributed to a hypersensitivity-type
reaction to Cremophor® or history of hypersensitivity-type reaction to polysorbate 80
or other components of the formulation of Oraxol

- Other severe acute or chronic medical (including bone marrow suppressive diseases) or
psychiatric condition or laboratory abnormality that may increase the risk associated
with study participation, impede the ability of the subject to complete all
protocol-specified activities, or may interfere with the interpretation of study
results and, in the judgment of the Investigator, would make the subject inappropriate
for this study