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

Inclusion Criteria

• 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.
• Documented progression on or following most recent systemic chemotherapy regimen (not required for chemotherapy-naïve patients), within 4 months prior to screening
• Measurable disease by RECIST v1.1
• Age of 18 years or older; in addition, patients age 12 to 17 years may enroll beginning in Cohort 2 if weight ≥ 40 kg
• 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 patient's pre-study baseline (except alopecia or neuropathy)
• Adequate organ function
• Willingness and ability to consent (and assent if under age 18) for self to participate in study
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
• Angiosarcoma tumor specimen, if available
• 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
• 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

• Prior treatment with TRC105
• Prior treatment with any VEGF inhibitor
• More than two prior lines (may be combination regimens) of chemotherapy for angiosarcoma (neoadjuvant/adjuvant treatment does not count as a line of treatment)
• Current treatment or participation on another therapeutic clinical trial
• Women who are pregnant or breastfeeding
• Receipt of systemic anticancer therapy, including investigational agents, within 5 times the agent's elimination half-life of starting study treatment
• 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
• 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 150 or diastolic > 100 mm Hg on the average of the 3 most recent BP readings. Anti-hypertensives may be started prior to randomization.
• Ascites or pleural effusion requiring intervention or that required intervention or recurred within three months prior to randomization
• Pericardial effusion (except trace effusion identified by echocardiogram) within three months prior to randomization
• History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patien