TRC105 for Liver Cancer That Has Not Responded to Sorafenib
- 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.
- To test the safety and effectiveness of TRC105 to treat liver cancer that has not responded to standard therapy.
- 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.
- 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.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of TRC105 in Patients With Hepatocellular Carcinoma (HCC) Who Have Progressed on Sorafenib|
- Time to Tumor Progression (TTP) for TRC105 in Hepatocellular Carcinoma (HCC). [ Time Frame: 2 years ] [ Designated as safety issue: No ]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).
- Number of Participants With Adverse Events [ Time Frame: 25 months, 15 days ] [ Designated as safety issue: Yes ]here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Experimental: TRC105 in Liver Cancer
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.
- 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).
-To evaluate time to tumor progression (TTP) for TRC105 in HCC.
- 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.
- 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).
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01375569
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Tim F Greten, M.D.||National Cancer Institute (NCI)|