Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)

TRC105 is a monoclonal antibody that binds to endoglin, an angiogenic target highly expressed
on the tumor vessels and tumor cells in gestational trophoblastic neoplasia (GTN).
Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that
inhibits angiogenesis and extends survival in patients with a wide variety of solid tumor
types. TRC105 has been well tolerated as a single agent and when combined with bevacizumab.
These antibodies may be efficacious in refractory GTN, a tumor type that is highly vascular
and has been shown to densely express endoglin.

Inclusion Criteria:

1. Willingness and ability to consent for self to participate in study

2. Willingness and ability to comply with study procedures

3. Elevated serum hCG (in cases of choriocarcinoma); elevated hCG or measurable disease
(in cases of PSTT or ETT)

4. Histologically proven trophoblastic neoplasia, or clinically demonstrated
trophoblastic neoplasia that has progressed following treatment with at least one
chemotherapy regimen that included 2 or more chemotherapy agents.

5. Age of 16 years or older

6. ECOG performance status ≤ 1

7. Resolution of all acute adverse events resulting from prior cancer therapies to NCI
CTCAE grade ≤ 1 or baseline

8. Adequate organ function

Exclusion Criteria:

1. Male

2. Prior treatment with TRC105

3. . Current treatment on another therapeutic clinical trial

4. Uncontrolled chronic hypertension defined as systolic > 150 or diastolic > 90 despite
optimal therapy

5. Significant pericardial effusion, pleural effusion, or ascites

6. Active bleeding or pathologic condition that carries a high risk of bleeding

7. Tumors located in the central chest or other location where bleeding is associated
with high morbidity

8. Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day
of study therapy

9. Angina, MI, 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 the past 6
months. Deep venous thrombosis within 6 months, unless the patient is therapeutically
anti-coagulated for at least 2 weeks. In this situation, low molecular weight heparin
is preferred

10. Known active viral or nonviral hepatitis

11. Pregnant or actively breastfeeding without intention to discontinue prior to
initiation of study

12. Open wounds or unhealed fractures within 28 days of starting study treatment

13. History of peptic ulcer disease or erosive gastritis within the past 6 months, unless
treated for the condition and complete resolution has been documented by
esophagogastroduodenoscopy (EGD) within 28 days of starting study treatment

14. History of gastrointestinal perforation or fistula in the past 6 months, or while
previously on antiangiogenic therapy, unless underlying risk has been resolved

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

16. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or may
interfere with the interpretation of study results and, in the judgment of the
Investigator, would make the patient inappropriate for this study

17. 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 brain
edema for at least 28 days

18. Receipt of systemic anticancer therapy, including investigational agents, within 28
days of starting study treatment. If anticancer therapy was given within 28 days of
starting study treatment, patients may be included if 5 times the elimination
half-life of the drug has passed

19. 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 starting study treatment or those patients who have not recovered
adequately from side effects of such therapy

20. Major surgical procedure or significant traumatic injury within 6 weeks prior to study
registration or not fully recovered from any such procedure