Sorafenib and TRC105 in Hepatocellular Cancer
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.
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.
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.
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, and will have an examination of the esophagus to look for problems with blood vessels.
Participants will receive sorafenib tablets twice every day, in the morning and at night, with a full glass of water.
Participants will receive TRC105 infusions once every two weeks on days 1, 8, 15, and 22 of a 28-day cycle. Participants will also receive two doses of dexamethasone the day before the infusion to prevent possible side effects.
At each visit during the first cycle, participants will have a physical examination and blood tests. Participants will continue to have blood tests and a urine test every cycle to monitor the effects of treatment, including tests of kidney function. Participants will have imaging studies after every two cycles to evaluate the results of treatment, and may also provide tumor samples for study.
Treatment will continue as long as the tumor does not grow and side effects remain tolerable.
Adenoma, Liver Cell
Liver Neoplasms, Experimental
Drug: TRC 105
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of TRC105 in Combination With Sorafenib in Hepatocellular Carcinoma (HCC)|
- Phase I: To establish the maximum tolerated dose (MTD) of TRC105 when given with standard-dose sorafenib for HCC. [ Time Frame: Complete ] [ Designated as safety issue: Yes ]
- Phase II: To evaluate time to progression (TTP) for the combination of TR105 with sorafenib in HCC. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To evaluate overall response rate (ORR) as determined by both standard and EASL-modified RECIST criteria [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To evaluate the immunogenicity of TRC105 as measured by humanantichimeric antibody (HACA) and human antimouse antibodyformation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To evaluate the safety of the combination of TRC105 and sorafenibin HCC. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To determine progression-free survival (PFS) and overall survival (OS) for TRC105 and sorafenib in HCC. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||February 2011|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
15 mg/kg TRC105 IV every 2 weeks and 400 mg sorafenib PO twice per day
Drug: TRC 105
15 mg/kg IV every 2 weeksDrug: Sorafenib
400 mg bid continuously in a 28 days cycle
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01306058
|Contact: Suzanne Fioravanti, R.N.||(301) firstname.lastname@example.org|
|Contact: Tim F Greten, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Tim F Greten, M.D.||National Cancer Institute (NCI)|