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

NCT02664961 | Terminated Phase 2 Results

• 1 other identifier: 105GTN201
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

TRC105; CD105; Endoglin; Angiogenesis inhibitor; GTN; Bevacizumab; Avastin

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Progression-Free Survival (PFS)

  8 weeks

• Overall Response Rate on Bevacizumab Alone

  8 weeks

• Maximum Plasma Concentration (Cmax) of TRC105.

  cycle 2 day 1 (28 days after initiation of dosing)

• TRC105 Immunogenicity as Assessed by Anti-Product Antibody (APA).

  8 weeks

• Frequency and Severity of Adverse Events

  20 months

Study Arms (1)

TRC105 and/or bevacizumab

EXPERIMENTAL

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.

Drug: TRC105; Drug: Bevacizumab

Interventions

TRC105 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.

Also known as: Chimeric Antibody (TRC105) to CD105

TRC105 and/or bevacizumab

Bevacizumab DRUG

Bevacizumab will be dosed every two weeks.

Also known as: Avastin

TRC105 and/or bevacizumab

Eligibility Criteria

• Age: 16 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Willingness and ability to consent for self to participate in study
• Willingness and ability to comply with study procedures
• Elevated serum hCG (in cases of choriocarcinoma); elevated hCG or measurable disease (in cases of PSTT or ETT)
• 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.
• Age of 16 years or older
• ECOG performance status ≤ 1
• Resolution of all acute adverse events resulting from prior cancer therapies to NCI CTCAE grade ≤ 1 or baseline
• Adequate organ function

You may not qualify if:

• Male
• Prior treatment with TRC105
• Current treatment on another therapeutic clinical trial
• Uncontrolled chronic hypertension defined as systolic \> 150 or diastolic \> 90 despite optimal therapy
• Significant pericardial effusion, pleural effusion, or ascites
• Active bleeding or pathologic condition that carries a high risk of bleeding
• Tumors located in the central chest or other location where bleeding is associated with high morbidity
• Thrombolytic use (except to maintain i.v. catheters) within 10 days prior to first day of study therapy
• 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
• Known active viral or nonviral hepatitis
• Pregnant or actively breastfeeding without intention to discontinue prior to initiation of study
• Open wounds or unhealed fractures within 28 days of starting study treatment
• 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
• History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

Sponsors & Collaborators

• Tracon Pharmaceuticals Inc.: lead

Study Sites (3)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Gestational Trophoblastic Disease; Choriocarcinoma; Trophoblastic Tumor, Placental Site

Interventions

carotuximab; Bevacizumab

Condition Hierarchy (Ancestors)

Trophoblastic Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Pregnancy Complications, Neoplastic; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Monitor
• Organization: TRACON Pharmaceuticals

ctheuer@traconpharma.com

8585500780

Study Officials

• Charles Theuer, MD, PhD

  Tracon Pharmaceuticals Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2016
• First Posted: January 27, 2016
• Study Start: March 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: November 1, 2018
• Last Updated: July 23, 2019
• Results First Posted: June 4, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)