Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
Condition: Gestational Trophoblastic Neoplasia; Choriocarcinoma; Placental Site Trophoblastic Tumor; Epithelioid Trophoblastic Tumor
MeSH terms: Neoplasms; Choriocarcinoma; Trophoblastic Neoplasms; Gestational Trophoblastic Disease; Trophoblastic Tumor, Placental Site
Intervention: TRC105; Bevacizumab
Intervention description: Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing.; Bevacizumab will be dosed every two weeks.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 16 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: TRC105; CD105; Endoglin; Angiogenesis inhibitor; GTN; Bevacizumab; Avastin

Summary:

      The purpose of the study is to determine the overall response rate of single agent TRC105 and
      the combination of TRC105 and bevacizumab in patients with refractory GTN (including
      choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic
      tumor (ETT)). Up to 30 patients will be treated.
    

Eligibility criteria:

        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