Clinical Trial: Sorafenib and TRC105 in Hepatocellular Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of TRC105 in Combination With Sorafenib in Hepatocellular Carcinoma (HCC)

Brief Summary:

Background:

Sorafenib is a drug that has been approved to treat kidney and liver cancer (hepatocellular carcinoma, or HCC) and has been shown to prolong survival in patients with HCC. It works by slowing the spread of cancer cells, but it does not fully prevent the cancer from growing again. Researchers are interested in combining sorafenib with the experimental drug TRC105, which has been designed to block the growth of blood vessels that lead to tumor growth, in order to determine whether this drug combination stops tumor growth and reduces tumor size better than sorafenib alone.

Objectives:

To determine the safety and effectiveness of the combination of sorafenib and TRC105 as a treatment for hepatocellular cancer that has not responded to other treatments.

Eligibility:

Individuals at least 18 years of age who have been diagnosed with hepatocellular cancer that has not responded to other treatments, and who are not considered to be candidates for liver transplantation. Patients cannot be receiving anticoagulant therapy with the exception of low dose aspirin. No history of bleeding problems or peptic ulcer disease.

Design:

Participants will be screened with a full medical history and physical examination, blood and urine tests, and tumor imaging studies. Participants will have a tumor biopsy or provide previously collected tumor tissue for study. An examination of the esophagus to look for problems with blood vessels will be completed in patients with a history of cirrhosis.

Participants will receive sorafenib tablets twice ev

Detailed Summary:

Background:

  • Worldwide, hepatocellular carcinoma (HCC) is the fifth most common malignancy with a median survival of 6-9 months. The SHARP study established sorafenib as a standard consideration in this disease and set the bar for future studies of systemic therapy.
  • TRC105 is a chimeric anti-angiogenic monoclonal antibody that binds CD105, a transmembrane receptor selectively expressed by proliferating endothelial cells. TRC105 binds to CD105-expressing endothelial cells and mediates growth inhibition, apoptosis and antibody-dependent cell-mediated cytotoxicity (ADCC).

Objectives:

Primary:

  • Phase I: To establish the maximum tolerated dose (MTD) of TRC105 when given with standard-dose sorafenib for HCC.
  • Phase II:To determine the estimate response rate according to RECIST criteria for the combination of TRC105 with sorafenib in HCC.

Eligibility:

  • Histologically or cytologically confirmed diagnosis of HCC.
  • Childs-Pugh A or B (7 points) cirrhosis is allowed.
  • Patients must have disease that is not amenable to potentially curative resection, radiofrequency ablation, or liver transplantation.
  • In phase I, prior systemic therapy is allowed.
  • In phase II, prior systemic therapy for HCC (including sorafenib) is allowed.
  • No history of bleeding varices in previous 1 year (unless subsequent liver
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome:

    • Phase I: To establish the maximum tolerated dose (MTD) of TRC105 when given with standard-dose sorafenib for HCC. [ Time Frame: Complete ]
    • Phase II: To evaluate time to progression (TTP) for the combination of TR105 with sorafenib in HCC. [ Time Frame: 2 years ]


    Original Primary Outcome:

    • Phase I: To establish the maximum tolerated dose (MTD) of TRC105 when given with standard-dose sorafenib for HCC. [ Time Frame: 6/30/2012 ]
    • Phase II: To evaluate time to progression (TTP) for the combination of TR105 with sorafenib in HCC. [ Time Frame: 1/31/2014 ]


    Current Secondary Outcome:

    • To evaluate overall response rate (ORR) as determined by both standard and EASL-modified RECIST criteria [ Time Frame: 2 years ]
    • To evaluate the immunogenicity of TRC105 as measured by humanantichimeric antibody (HACA) and human antimouse antibodyformation [ Time Frame: 2 years ]
    • To evaluate the safety of the combination of TRC105 and sorafenibin HCC. [ Time Frame: 2 years ]
    • To determine progression-free survival (PFS) and overall survival (OS) for TRC105 and sorafenib in HCC. [ Time Frame: 2 years ]
    • To perform correlative studies assessing 1) potential biomarkers ofresponse to angiogenic therapy, 2) changes in frequency andfunction of immune cells upon treatment and 3) molecularcharacterization of tumors. [ Time Frame: 2 years ]


    Original Secondary Outcome:

    • To evaluate the safety [ Time Frame: 1/31/2014 ]
    • To evaluate the immunogenicity [ Time Frame: 1/31/2014 ]
    • To evaluate the overall response rate [ Time Frame: 1/31/2014 ]


    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: February 26, 2011
    Date Started: February 11, 2011
    Date Completion: January 31, 2018
    Last Updated: April 11, 2017
    Last Verified: April 7, 2017