NCT01975519

A Phase 1B Dose-escalation and Phase 2a Study of Carotuximab (TRC105) in Combination With Pazopanib in Patients With Advanced Soft Tissue Sarcoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 111 (actual)
• Sponsor: Tracon Pharmaceuticals Inc. · Industry
• Sex: All
• Age: 12 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

The purpose of the phase 1b portion is to evaluate safety and tolerability and determine a recommended phase 2 dose for TRC105 when added to standard dose pazopanib in patients with advanced soft tissue sarcoma. Up to 30 patients will be treated. The purpose of the phase 2 portion is to estimate the PFS of patients with advanced soft tissue sarcoma by RECIST 1.1 and estimate ORR in a separate cohort of patients with angiosarcoma by RECIST 1.1. Up to 89 patients will be treated in phase 2, including two cohorts of up to 13 patients with angiosarcoma.

Detailed description

Pazopanib is an oral inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptor VEGFR-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. Pazopanib is approved for the treatment of advanced soft tissue sarcoma, following progression on one prior systemic therapy, based on improved progression free survival. TRC105 is an antibody to CD105, an important angiogenic target on vascular endothelial cells that is distinct from VEGFR. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR. In a phase 1 study of advanced solid tumors, TRC105 therapy caused a global reduction in angiogenic biomarkers and reduced tumor burden at doses that were well-tolerated. 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 potentiates bevacizumab and VEGFR tyrosine kinases (VEGFR TKI) in preclinical models. By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR TKIs and could represent a major advance in cancer therapy. Together, the use of TRC105 with pazopanib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with pazopanib alone.

Conditions

• Advanced Soft Tissue Sarcoma

Interventions

Type	Name	Description
DRUG	TRC105 and Pazopanib	Weekly TRC105 in combination with standard dose Pazopanib.

Timeline

• Start date: 2013-12-10
• Primary completion: 2019-03-11
• Completion: 2019-03-11
• First posted: 2013-11-04
• Last updated: 2020-05-20
• Results posted: 2020-05-12

Locations

9 sites across 1 country: United States