| Eligibility |
Inclusion Criteria:
- Willingness and ability to give informed consent, prior to any study-specific
procedures and willingness to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status =1
- Resolution of all acute AEs resulting from prior cancer therapies to National Cancer
Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE
v4.03) Grade =1 or to that subject's baseline
- 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
- Able to swallow pills whole and retain oral medications
- Sexually active male subjects including men who are sterile (including vasectomy
confirmed by post vasectomy semen analysis) must agree to use a condom with spermicide
and to not donate sperm from the time of Screening until 6 months following the last
dose of Oraxol
- Women 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 woman aged =45 years), OR women of childbearing potential who
test negative for pregnancy at time of enrollment based on serum pregnancy test must
be using a highly effective method of contraception from the time of Screening until 6
months following the last dose of Oraxol. Note: Highly effective methods of
contraception that result in a low failure rate (ie, <1% per year) when used
consistently and correctly include combined (estrogen and progestogen containing)
hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or
transdermal), progestogen-only hormonal contraception associated with inhibition of
ovulation (oral, injectable, or implantable), intrauterine device, intrauterine
hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual
abstinence. True abstinence, when in line with the preferred and usual lifestyle of
the subject, is considered a highly effective method only if defined as refraining
from heterosexual intercourse during the entire period of study participation and for
6 months post-Oraxol administration. The reliability of sexual abstinence needs to be
evaluated in relation to the duration of the clinical study and the preferred and
usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation,
symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of
contraception.
- 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. Participation in companion studies sponsored by local institutions,
including biological correlates, is permitted.
- 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.
Note: The following are not considered to be major procedures and are permitted before
treatment administration: thoracentesis, paracentesis, catheter placement, port
placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic
ultrasonographic procedures, mediastinoscopy, skin biopsies, and imaging-guided biopsy
for diagnostic purposes
- 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
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