Clinical Trial: A RANDOMIZED PHASE 3 TRIAL OF TRC105 AND PAZOPANIB VERSUS PAZOPANIB ALONE IN PATIENTS WITH ADVANCED ANGIOSARCOMA

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A RANDOMIZED PHASE 3 TRIAL OF TRC105 AND PAZOPANIB VERSUS PAZOPANIB ALONE IN PATIENTS WITH ADVANCED ANGIOSARCOMA (TAPPAS)

Brief Summary: This is a study of TRC105 in combination with standard dose pazopanib compared to single agent pazopanib in patients with angiosarcoma not amenable to curative intent surgery (e.g., metastatic or bulky disease, and disease for which surgical resection would carry an unacceptable risk to the patient) who have not received pazopanib or TRC105 previously.

Detailed Summary:

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.


Sponsor: Tracon Pharmaceuticals Inc.

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.


Original Secondary Outcome:

  • 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 compare duration of objective response (DR) of TRC105 and pazopanib vs single agent pazopanib in patients with unresectable angiosarcoma [ Time Frame: 24 months ]
    Duration of response (DR) is defined as the time from first objective response (CR or PR) to the date of the first documented tumor progression, as determined by Central Radiographic Review according to RECIST 1.1 or date of death due to any cause, whichever occurs first.
  • 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.


Information By: Tracon Pharmaceuticals Inc.

Dates:
Date Received: November 29, 2016
Date Started: February 13, 2017
Date Completion: December 2018
Last Updated: February 16, 2017
Last Verified: February 2017