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

Non Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03780010
• Other study ID #: 105LC101
• Status: Completed
• Phase: Phase 1
• Start date: September 2015
• Est. completion date: June 2019

Study information

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

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Tracon Pharmaceuticals Inc.	University of Alabama at Birmingham

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall RECIST 1.1 Response Rate	Response rate determined according to RECIST 1.1 criteria	6 months
Secondary	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
Secondary	Median Progression Free Survival	Median duration of progression free survival according to RECIST 1.1 criteria	months
Secondary	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
Secondary	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