Clinical trial NCT02664961: Study of TRC105 and Bevacizumab in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
Official title: A Phase 2A Study of TRC105 (With Option to Add Bevacizumab) in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Gestational Trophoblastic Neoplasia
Choriocarcinoma
Placental Site Trophoblastic Tumor
Epithelioid Trophoblastic Tumor
Keywords: TRC105
CD105
Endoglin
Angiogenesis inhibitor
GTN
Bevacizumab
Avastin
Lead sponsor: Tracon Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-27
Enrollment: 3
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab
timeFrame: 8 weeks
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 8 weeks
measure: Overall Response Rate on Bevacizumab Alone
timeFrame: 8 weeks
measure: Maximum Plasma Concentration (Cmax) of TRC105.
timeFrame: cycle 2 day 1 (28 days after initiation of dosing)
measure: TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).
timeFrame: 8 weeks
measure: Frequency and Severity of Adverse Events
timeFrame: 20 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
Study officials:
affiliation: Tracon Pharmaceuticals Inc.
name: Charles Theuer, MD, PhD
role: STUDY_DIRECTOR
References: