TRC105 for Liver Cancer That Has Not Responded to Sorafenib

Phase 2

Completed

Conditions: Hepatocellular Carcinoma
Hepatocellular Cancer
Carcinoma, Hepatocellular

Interventions: Drug: TRC105

Registration Number: NCT01375569

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

- TRC105 is an experimental cancer drug. It is designed to slow or stop the growth of tumors. It does this by preventing the growth of new blood vessels that feed these tumors. People with hepatocellular carcinoma (or liver cancer) sometimes do not respond to standard treatments. This includes the cancer drug sorafenib.

Objectives:

- To test the safety and effectiveness of TRC105 to treat liver cancer that has not responded to standard therapy.

Eligibility:

* People at least 18 years of age who have hepatocellular carcinoma (or liver cancer) that has not responded to standard therapy. Participants also will not be eligible for a liver transplant.

* No anticoagulation therapy is allowed with the exception of low-dose aspirin.

* No history of bleeding disorders, peptic ulcer disease or gastritis.

Design:

* Participants will have a physical exam and medical history. They will also have blood and urine tests, and imaging studies.

* Participants will receive TRC105 once a week. They will also have two daily doses of a steroid the day before each treatment. This will help prevent known side effects.

* Participants will be monitored with blood and urine tests. They will also have imaging studies every two months to study the effect of the drug on tumor growth.

* Participants will continue to have TRC105 as long as they do not have severe side effects and their liver cancer stops growing or shrinks. After stopping TRC105, they will have yearly visits with physical exams and blood tests.

Detailed Description: Background:

* Worldwide, hepatocellular carcinoma (HCC) is the fifth most common malignancy with a median survival of 6-9 months. The Study of Heart and Renal Protection (SHARP) study established Sorafenib as a standard consideration in this disease and set the bar for future studies of systemic therapy. There is no standard therapy for patients whose disease has progressed despite Sorafenib therapy.

* TRC105 is a chimeric, anti-angiogenic monoclonal antibody that binds CD105, a transmembrane receptor overexpressed 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:

-To evaluate time to tumor progression (TTP) for TRC105 in HCC.

Secondary:

* To evaluate safety of TRC105 in HCC.

* To evaluate the immunogenicity of TRC105 as measured by human antichimeric antibody (HACA) and human antimouse antibody formation.

* To evaluate anti-tumor response as determined by standard and European Association for the Study of the Liver (EASL) -modified Response Evaluation Criteria in Solid Tumors (RECIST) response criteria.

* To perform correlative studies assessing potential biomarkers of response to TRC105.

Eligibility:

* Histologically or cytologically confirmed diagnosis of HCC.

* Childs-Pugh A or B (7 points) cirrhosis only is allowed.

* Patients must have disease that is not amenable to potentially curative resection.

* Patients must have progressed on or been intolerant of prior sorafenib therapy.

* No history of bleeding varices (unless subsequent liver transplant). All patients must have had endoscopic evaluation within 6 months of starting study.

* No history of bleeding varices in previous 1 year (unless subsequent liver transplant). No anti-coagulation (except low-dose aspirin).

Design:

* This is a single-arm phase II study of TRC105 in patients with HCC.

* TRC105 will be administered as an intravenous infusion every two weeks. Patients will be re-staged every 8 weeks.

* The primary endpoint of the study will be Time to Tumor Progression (TTP). The primary purpose of this study is to evaluate the ability of TRC105 as a second line treatment to improve upon the time to progression (TTP) of patients with refractory HCC.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TRC105 in Liver Cancer	TRC105	TRC105 is an experimental cancer drug designed to slow or stop the growth of tumors. It does this by preventing the growth of new blood vessels that feed these tumors. This drug is being used to test the safety and effectiveness to treat liver cancer that has not responded to standard therapy. TRC105 will be given as an intravenous infusion every two weeks.

Primary Outcome Measures

Name	Time	Method
Time to Tumor Progression (TTP) for TRC105 in Hepatocellular Carcinoma (HCC).	2 years	Time to tumor progression is defined as the proportion of participants who are progression free after 4 months on study. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progressions).

Secondary Outcome Measures

Name	Time	Method
Count of Participants With Adverse Events	25 months, 15 days	here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.