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

NCT ID: NCT02664961

Last Updated: 2019-07-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2018-11-30

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.

Conditions

Gestational Trophoblastic Neoplasia; Choriocarcinoma; Placental Site Trophoblastic Tumor; Epithelioid Trophoblastic Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TRC105 and/or bevacizumab

All subjects will begin by receiving single agent TRC105 weekly. In the case of a complete response to single agent TRC105, subjects will continue to receive single agent TRC105 for at least 3 months following complete response. In the case of a partial response (without a complete response) to single agent TRC105, bevacizumab every two weeks will be added. In the absence of a partial or complete response to single agent TRC105, subjects will receive single agent bevacizumab every two weeks. In the absence of a complete response to single agent bevacizumab, or for subjects who have documented disease progression on a prior bevacizumab containing regimen, subjects will receive TRC105 weekly and bevacizumab every two weeks.

Group Type: EXPERIMENTAL

TRC105

Intervention Type: DRUG

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

Intervention Type: DRUG

Bevacizumab will be dosed every two weeks.

Interventions

TRC105

Subjects will begin by receiving TRC105 weekly. Subjects who achieve a complete response on single agent TRC105 may transition to every two week dosing.

Intervention Type: DRUG

Bevacizumab

Bevacizumab will be dosed every two weeks.

Intervention Type: DRUG

Other Intervention Names

Chimeric Antibody (TRC105) to CD105; Avastin

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Tracon Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Theuer, MD, PhD

Role: STUDY_DIRECTOR

Tracon Pharmaceuticals Inc.

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Ohio State University

Columbus, Ohio, United States

UT Southwestern

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

105GTN201

Identifier Type: -

Identifier Source: org_study_id