Study of TRC105 + Paclitaxel/Carboplatin and Bevacizumab in Patients With NSCLC

A Phase 1b Dose-escalation Study of TRC105 in Combination With Paclitaxel/Carboplatin and Bevacizumab in Patients With Stage 4 Non-Squamous Cell Lung Cancer

This is a single center, open-label, nonrandomized, phase 1b, dose-finding study of TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: TRC105

Detailed Description

Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF) that inhibits angiogenesis and extends survival in non-squamous non-small cell lung cancer (NSCLC) patients when given with carboplatin and paclitaxel. TRC105 is an antibody to endoglin, an essential angiogenic target expressed on proliferating endothelial cells that is distinct from the VEGFR and overexpressed in response to VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of antibodies and small molecules that target the VEGFR. In a phase 1b study, the combination of TRC105 and bevacizumab produced radiographic reductions in tumor volume in bevacizumab-refractory patients, and was well tolerated. TRC105 was also well tolerated with chemotherapy in a trial with capecitabine in breast cancer patients. The use of TRC105 with bevacizumab and paclitaxel/carboplatin may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with bevacizumab and paclitaxel/carboplatin alone.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Stage 4 Non-Squamous Cell Lung Cancer that has not been treated previously with systemic chemotherapy or bevacizumab, but may have received prior targeted treatment (e.g., alk1 inhibitor)
• ECOG performance status ≤ 1
• Measurable disease by RECIST

Key Exclusion Criteria:

• Non-small cell lung cancer of squamous histology
• Current treatment on another therapeutic clinical trial
• 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 study registration or those patients who have not recovered adequately from side effects of such therapy
• Active bleeding or pathologic condition that carries a high risk of bleeding (e.g. hereditary hemorrhagic telangiectasia). Patients who have been uneventfully anti-coagulated with low molecular weight heparin are eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRC105 + B + P + C; TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC.	Drug: TRC105; Dose-finding study of TRC105 in combination with standard dose bevacizumab and paclitaxel/carboplatin in treatment-naive patients with stage IV non-squamous NSCLC.; Other Names: Bevacizumab; Carboplatin; Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events	Incidence of treatment-emergent (i.e. TRC105, bevacizumab, paclitaxel and/or carboplatin) adverse events by CTCAE v4.03	from screening until completion of follow-up, on average 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall RECIST 1.1 Response Rate	Response rate determined according to RECIST 1.1 criteria	6 months
Percent of Patients With Progression-free Survival (PFS) at 6 Months	Number of patients with progression-free survival at 6 months determined according to RECIST 1.1 criteria	6 months
Median Progression Free Survival	Median duration of progression free survival according to RECIST 1.1 criteria	months
Pharmacokinetic Profile of TRC105 When Given With Bevacizumab and Paclitaxel/Carboplatin	Trough serum TRC105 pharmacokinetic concentrations at steady state (cycle 3 day 1) will be measured using validated ELISA methods.	3 months
Number of Patients Who Have TRC105 Positive Anti-Product Antibodies	Anti-product antibody concentrations will be measured using validated ELISA methods. Anti-product antibody concentrations will be evaluated in the context of pharmacokinetic parameters and AE profiles.	6 months

Collaborators and Investigators

• Sponsor: Tracon Pharmaceuticals Inc.
• Collaborators: University of Alabama at Birmingham
• Investigators: Study Director: Charles Theuer, MD, TRACON Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): October 28, 2019
• Last Update Submitted That Met QC Criteria: October 4, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: 105LC101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No