A RANDOMIZED PHASE 3 TRIAL OF TRC105 AND PAZOPANIB VERSUS PAZOPANIB ALONE IN PATIENTS WITH ADVANCED ANGIOSARCOMA (TAPPAS)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A RANDOMIZED PHASE 3 TRIAL OF TRC105 AND PAZOPANIB VERSUS PAZOPANIB ALONE IN PATIENTS WITH ADVANCED ANGIOSARCOMA (TAPPAS)|
- To compare PFS of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma [ Time Frame: 24 months ]PFS is defined as time from randomization to either first disease progression (per independent radiology review of images by RECIST 1.1) or death from any cause.
- To compare the objective response rate (ORR) of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma [ Time Frame: 24 months ]Objective response rate (ORR) is defined as the number of patients with a best response of complete response (CR) or partial response (PR) divided by the number of randomized patients. ORR is defined as the best response designation recorded between the date of randomization and the date of documented progression, as determined by Central Radiographic Review according to RECIST 1.1, or date of subsequent therapy, whichever occurs first.
- To compare overall survival (OS) of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma [ Time Frame: 24 months ]Overall Survival (OS) is defined as the time between the date of randomization and the date of death from any cause. Overall survival will be calculated in days as: Date of Death - Date of Randomization +1.
- To assess the overall safety and tolerability of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma [ Time Frame: 24 months ]Type, incidence, severity (graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 4.03), timing, seriousness, and relatedness of AEs and laboratory abnormalities.
- To characterize patient reported outcomes between the two arms of the study [ Time Frame: 24 months ]Patient reported outcomes as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L) and the EORTC QLQ-C30 questionnaire.
- To characterize the pharmacokinetic (PK) profile of TRC105 and pazopanib between the two arms of the study [ Time Frame: 24 months ]TRC105 and pazopanib pharmacokinetic (PK) concentrations will be measured using validated methods from peak and trough samples.
- To characterize the immunogenicity of TRC105 [ Time Frame: 24 months ]Anti-TRC105 antibodies will be measured using validated methods and anti-drug antibody (ADA) titers will be correlated with PK parameters and AEs.
|Actual Study Start Date:||February 13, 2017|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Experimental: TRC105 plus votrient
weekly TRC105 i.v. in combination with standard dose votrient by mouth, once daily
Other Names:Drug: Votrient
Other Name: pazopanib
Active Comparator: votrient
standard dose votrient by mouth, once daily
Other Name: pazopanib
TRC105 (carotuximab) is a monoclonal antibody to endoglin (CD105), an essential angiogenic target highly expressed on tumor vessels that is distinct from VEGFR. Endoglin is also expressed directly on tumor cells in angiosarcoma and is upregulated following VEGF inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models and complements the activity of bevacizumab and multi-kinase inhibitors that target the VEGFR.
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.
By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the potential to complement VEGFR tyrosine kinase inhibitors (TKIs) and could represent a major advance in the treatment of angiosarcoma. Together, the use of TRC105 with pazopanib may result in more effective angiogenesis inhibition and improved clinical efficacy over that seen with pazopanib alone.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02979899
|Contact: TRACON Clinical Trialsfirstname.lastname@example.org|
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|Study Director:||Richard Yocum, MD||TRACON Pharmaceuticals|