Phase II Study Evaluating the Role of Pazopanib in Angiosarcoma

Inclusion Criteria:

- Subjects must provide written informed consent and Health Insurance Portability and
Accountability Act (HIPAA) consent prior to performance of study-specific procedures
or assessments and must be willing to comply with treatment and follow up

- Note: informed consent may be obtained prior to start of the specified screening
window

- Note: procedures conducted as part of the subject's routine clinical management
(e.g., blood count, imaging study such as bone scan) and obtained prior to
signing of informed consent may be utilized for screening or baseline purposes
provided these procedures are conducted as specified in the protocol

- Histologically or cytologically proven diagnosis of advanced stage angiosarcoma that
is not amenable to treatment with curative intent; specify site of origin as
cutaneous vs. non-cutaneous

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

- Must have measurable disease per Response Evaluation Criteria In Solid Tumors
(RECIST) 1.1 or cutaneous disease amenable to serial measurements should be present;
a measurable lesion is defined as a lesion that can be accurately measured in at
least one dimension with the longest diameter >= 10 mm with computed tomography (CT)
scan; lesions that have been treated with therapeutic intent will be considered
measurable if they have increased in size by more than 20%

- Failed at least 1 standard regimen for unresectable angiosarcoma (excluding adjuvant
or neo-adjuvant therapy)

- Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

- Hemoglobin >= 9 g/dL (5.6 mmol/L)

- Platelets >= 100 X 10^9/L

- International normalized ratio (INR) =< 1.2 X upper limit of normal (ULN)

- Activated partial thromboplastin time (aPTT) =< 1.2 X ULN

- Total bilirubin =< 1.5 X ULN (may not have abnormalities in both bilirubin and
transaminases)

- Alanine amino transferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X ULN
(may not have abnormalities in both bilirubin and transaminases)

- Serum creatinine =< 1.5 mg/dL (133 umol/L)

- Or, if serum creatinine > 1.5 mg/dL: calculated creatinine clearance (ClCR) > 50
mL/min

- Urine Protein to Creatinine Ratio (UPC) < 1

- Able to swallow pills whole and retain oral medication

- A female is eligible to enter and participate in this study if the following apply:

- Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
including any female who has had:

- A hysterectomy

- A bilateral oophorectomy (ovariectomy)

- A bilateral tubal ligation

- Is post-menopausal

- Subjects not using hormone replacement therapy (HRT) must have experienced total
cessation of menses for >= 1 year and be greater than 45 years in age, OR, in
questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and
an estradiol value < 40pg/mL (< 140 pmol/L)

- Subjects using HRT must have experienced total cessation of menses for >= 1 year and
be greater than 45 years of age OR have had documented evidence of menopause based on
FSH and estradiol concentrations prior to initiation of HRT

- Childbearing potential, including any female who has had a negative serum pregnancy
test within 2 weeks prior to the first dose of study treatment and for 3 months after
the completion of treatment, preferably as close to the first dose as possible, and
agrees to use adequate contraception; acceptable contraceptive methods, when used
consistently and in accordance with both the product label and the instructions of
the physician, are as follow:

- Complete abstinence from sexual intercourse for 14 days before exposure to
investigational product, through the dosing period, and for at least 21 days
after the last dose of investigational product

- Oral contraceptive, either combined or progestogen alone

- Injectable progestogen

- Implants of levonorgestrel

- Estrogenic vaginal ring

- Percutaneous contraceptive patches

- Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure
rate of less than 1% per year

- Male partner sterilization (vasectomy with documentation of azoospermia) prior
to the female subject's entry into the study, and this male is the sole partner
for that subject

- Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault
caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)

- Female subjects who are lactating must discontinue nursing prior to the first dose of
study drug and refrain from nursing throughout the treatment period and for 14 days
following the last dose of study drug

- A male is eligible to enter and participate in this study if he and his female sexual
partner in the reproductive age group agree to use effective methods of contraception

Exclusion Criteria

- Prior malignancy

* Note: subjects who have been disease-free from their malignancy other than
angiosarcoma in the 2 years prior to first dose of study drug, and/or subjects with a
history of completely resected non-melanomatous skin carcinoma or successfully
treated in situ carcinoma are eligible

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medications for 3 months prior to first dose of study drug; screening
with CNS imaging studies (CT or magnetic resonance imaging [MRI]) is required only if
clinically indicated or if the subject has a history of CNS metastases

- Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding including, but not limited to:

- Active peptic ulcer disease

- Known intraluminal metastatic lesion/s with risk of bleeding

- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other
gastrointestinal conditions with increased risk of perforation

- History of abdominal fistula, gastrointestinal perforation, or intra abdominal
abscess within 28 days prior to beginning study treatment

- Clinically significant (> 1/2 teaspoon) hemoptysis or gastrointestinal
hemorrhage in the past 6 months

- Evidence of active bleeding or bleeding diathesis; recent hemoptysis (>= 1/2 teaspoon
of red blood within 8 weeks before first dose of study drug)

- Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product including, but not limited to:

- Malabsorption syndrome

- Major resection of the stomach or small bowel

- Corrected QT interval (QTc) > 480 msecs using Bazett's formula

- Left ventricular ejection fraction < 50%

- History of any one or more of the following cardiovascular conditions within the past
6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Coronary artery bypass graft surgery

- Symptomatic peripheral vascular disease

- Class III or IV congestive heart failure, as defined by the New York Heart
Association (NYHA)

- Poorly controlled hypertension (defined as systolic blood pressure [SBP] of >= 140
mmHg or diastolic blood pressure [DBP] of >= 90mmHg); Note: Initiation or adjustment
of antihypertensive medication(s) is permitted prior to study entry; following
antihypertensive medication initiation or adjustment, blood pressure (BP) must be
re-assessed three times at approximately 2-minute intervals; at least 24 hours must
have elapsed between anti-hypertensive medication initiation or adjustment and BP
measurement; these three values should be averaged to obtain the mean diastolic blood
pressure and the mean systolic blood pressure; the mean SBP / DBP ratio must be <
140/90 mmHg in order for a subject to be eligible for the study

- Cerebrovascular accident including transient ischemic attack (TIA), pulmonary
embolism or untreated deep venous thrombosis (DVT) within the past 6 months

* Note: subjects with recent DVT who have been therapeutically coagulated for at
least 6 weeks are eligible

- Major surgery or trauma within 28 days prior to first dose of investigational product
and/or presence of any non-healing wound, fracture, or ulcer (procedures such as
catheter placement not considered to be major surgery)

- Evidence of active bleeding or bleeding diathesis; recent hemoptysis (>= ½ teaspoon
of red blood within 8 weeks before first dose of study drug)

- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
(Note: tumor abutting the vessel is acceptable, but contiguous tumor and vessel is
not; CT with contrast is strongly recommended to evaluate such lesions)

- Abnormal serum calcium, magnesium, or potassium levels

- Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to study procedures

- Use of any prohibited medication within the timeframes

- Treatment with any of the following therapies:

- Radiation therapy, surgery or tumor embolization within 14 days prior to the
first dose of pazopanib hydrochloride OR

- Chemotherapy, immunotherapy, biologic therapy, investigational therapy or
hormonal therapy within 14 days or five half-lives of a drug (whichever is
longer) prior to the first dose of pazopanib

- Patients who require chronic use of strong cytochrome P450 3A4 (CYP3A4)
inhibitors or inducers including but not limited to grapefruit juice

- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 (except
hemoglobin value) and/or that is progressing in severity, except alopecia

- Previous exposure to pazopanib hydrochloride or a vascular endothelial growth factor
receptor (VEGFR) targeted kinase therapy, except for bevacizumab or VEGFR-Trap
(Aflibercept)

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib