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

Gestational Trophoblastic Neoplasia Clinical Trial

Official title:

A Phase 2A Study of TRC105 (With Option to Add Bevacizumab) in Patients With Refractory Gestational Trophoblastic Neoplasia (GTN)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02664961
• Other study ID #: 105GTN201
• Status: Terminated
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: November 2018

Study information

• Verified date: May 2019
• Source: Tracon Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: November 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Choriocarcinoma
• Epithelioid Trophoblastic Tumor
• Gestational Trophoblastic Disease
• Gestational Trophoblastic Neoplasia
• Neoplasms
• Placental Site Trophoblastic Tumor
• Trophoblastic Neoplasms

Intervention

Drug:
• 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.
• Bevacizumab
Bevacizumab will be dosed every two weeks.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Ohio State University	Columbus	Ohio
United States	UT Southwestern	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Tracon Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate on TRC105 Alone and on the Combination of TRC105 and Bevacizumab	Antitumor Activity of Single Agent TRC105 and the Combination of TRC105 and Bevacizumab will be assessed via RECIST 1.1 and by measuring circulating bHCG. Disease progression is defined as >20% increase (the absolute increase must be =10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.	8 weeks
Secondary	Progression-Free Survival (PFS)	Median Progression-Free Survival (PFS) via Serum hCG levels and response evaluation according to RECIST version 1.1 as a preliminary measure of the antitumor activity of TRC105. Disease progression is defined as >20% increase (the absolute increase must be =10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks. Patients must have screening (baseline) and at least one on study CT scan to be considered evaluable.	8 weeks
Secondary	Overall Response Rate on Bevacizumab Alone	Overall Response Rate on bevacizumab alone according to RECIST 1.1 in combination with serum hCG levels. Disease progression is defined as >20% increase (the absolute increase must be =10 IU/L) above the nadir on consecutive measurements separated by at least two weeks; Partial response is defined as a hCG decrease of 50% or more from starting value on consecutive measurements; Complete response will be defined as normalization of hCG on consecutive measurements separated by at least two weeks; Stable disease will be defined as the absence of response or progression on 3 consecutive measurements separated by at least two weeks.	8 weeks
Secondary	Maximum Plasma Concentration (Cmax) of TRC105.	Mean serum TRC105 concentrations were assessed at cycle 1 and cycle 2 on day 1, 8, 15, and 22 and on day 1 of every subsequent cycle using validated methods in order to determine the Cmax of TRC105	cycle 2 day 1 (28 days after initiation of dosing)
Secondary	TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).	Anti-Product Antibody (APA) concentrations will be measured using validated ELISA methods at the time points specified in the protocol. APA concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles. Number of patients with positive APA titers on study will be reported.	8 weeks
Secondary	Frequency and Severity of Adverse Events	Determine frequency and severity of adverse events as assessed by NCI CTCAE (Version 4.03)	20 months