Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma

Inclusion Criteria:

   1. Histologically-confirmed angiosarcoma that is not amenable to curative intent surgery
   (e.g., metastatic or bulky disease and disease for which surgical resection would
   carry an unacceptable risk to the patient). Pathology report will be reviewed by
   sponsor prior to randomization.

   2. Documented progression on or following most recent systemic chemotherapy regimen (not
   required for chemotherapy-naïve patients), within 4 months prior to screening

   3. Measurable disease by RECIST v1.1

   4. Age of 18 years or older; in addition, patients age 12 to 17 years may enroll
   beginning in Cohort 2 if weight ≥ 40 kg

   5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

   6. 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 patient's pre-study baseline (except alopecia or
   neuropathy)

   7. Adequate organ function

   8. Willingness and ability to consent (and assent if under age 18) for self to
   participate in study

   9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
   tests, and other study procedures

10. Angiosarcoma tumor specimen, if available

11. Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis)
   OR agree to use a condom with spermicide (refer to Section 2.6.1.3) and to not donate
   sperm during the study and for at least 180 days following last dose of TRC105 or
   pazopanib

12. 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 (i.e., no menstrual bleeding for
   more than 12 months in a women aged 45 years or more), 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, one of
   which must be highly effective, during the study and for at least 180 days after
   stopping TRC105 or pazopanib

Exclusion Criteria:

   1. Prior treatment with TRC105

   2. Prior treatment with any VEGF inhibitor

   3. More than two prior lines (may be combination regimens) of chemotherapy for
   angiosarcoma (neoadjuvant/adjuvant treatment does not count as a line of treatment)

   4. Current treatment or participation on another therapeutic clinical trial

   5. Women who are pregnant or breastfeeding

   6. Receipt of systemic anticancer therapy, including investigational agents, within 5
   times the agent's elimination half-life of starting study treatment

   7. Major surgical procedure or significant traumatic injury within 4 weeks prior to
   randomization and must have fully recovered from any such procedure or injury; planned
   surgery (if applicable) or the anticipated need for a major surgical procedure within
   the next six months. Note: the following are not considered to be major procedures and
   are permitted up to 7 days before randomization: Thoracentesis, paracentesis, port
   placement, laparoscopy, thoracoscopy, tube thoracostomy, bronchoscopy, endoscopic
   ultrasonographic procedures, mediastinoscopy, skin biopsies, and imaging-guided biopsy
   for diagnostic purposes

   8. Patients who have received wide field radiotherapy ≤ 28 days (defined as > 50% of
   volume of pelvic bones or equivalent) or limited field radiation for palliation < 14
   days prior to randomization

   9. Uncontrolled hypertension defined as systolic > 150 or diastolic > 100 mm Hg on the
   average of the 3 most recent BP readings. Anti-hypertensives may be started prior to
   randomization.

10. Ascites or pleural effusion requiring intervention or that required intervention or
   recurred within three months prior to randomization

11. Pericardial effusion (except trace effusion identified by echocardiogram) within three
   months prior to randomization

12. History of brain involvement with cancer, spinal cord compression, or carcinomatous
   meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated
   or resected lesions are permitted, provided the lesions are fully treated and
   inactive, patients are asymptomatic, and no steroids have been administered for at
   least 28 days prior to randomization

13. 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 6 months prior to randomization. Deep venous thrombosis within 3 months
   prior to randomization unrelated to a central venous catheter, unless the patient is
   anti-coagulated without the use of warfarin for at least 2 weeks prior to
   randomization. In this situation, low molecular weight heparin is preferred

14. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g.,
   hereditary hemorrhagic telangiectasia). Patients with bleeding cutaneous lesions not
   actively requiring transfusions are eligible. Patients who have been uneventfully
   anti-coagulated with low molecular weight heparin are eligible

15. Hemoptysis (> ½ teaspoon [2.5 mL] of bright red blood) within 6 months prior to
   randomization

16. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to
   randomization

17. Known active viral or nonviral hepatitis or cirrhosis

18. Peptic ulcer within the past 3 months prior to randomization, unless treated for the
   condition and complete resolution has been documented by esophagogastroduodenoscopy
   (EGD)

19. Presence of tumor(s) invading into the heart or great vessels (including carotid
   artery) or another location where bleeding is associated with high morbidity including
   patients with primary cardiac or great vessel angiosarcoma

20. Gastrointestinal perforation or fistula in the 6 months prior to randomization unless
   underlying risk has been resolved (e.g., through surgical resection or repair)

21. Presence of a malabsorption syndrome, gastrointestinal disorder, or gastrointestinal
   surgery that could affect the absorption of pazopanib

22. History of prior malignancy except adequately treated basal cell or squamous cell skin
   cancer or adequately treated, with curative intent, cancer from which the patient is
   currently in complete remission per Investigator's judgment; patients with history of
   breast cancer and no evidence of disease on hormonal therapy to prevent recurrence and
   patients with prostate cancer on adjuvant hormonal therapy with undetectable PSA are
   eligible

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

24. Active infection that requires systemic treatment

25. Concurrent use or receipt of a strong CYP3A4 inducer within 12 days prior to
   randomization or a strong CYP3A4 inhibitor within 7 days prior to randomization (see
   Table 10)

26. History of severe hypersensitivity reaction to any monoclonal antibody

27. 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 patient 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 patient inappropriate
   for this study