Sorafenib and TRC105 in Hepatocellular Cancer

Completed · Phase 1/Phase 2

Conditions studied: Hepatoma, Liver Neoplasms, Adenoma, Liver Cell, Carcinoma, Hepatocellular, Liver Neoplasms, Experimental

In brief

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 every day, in the morning and at night, with a full glass of water. Participants will receive TRC 105 infusions once every two weeks on days 1 and 15 of a 28 day cycle. 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.

Key facts

Study ID: NCT01306058
Run by: National Cancer Institute (NCI)
People needed: 27
Starts: 2011-02-11
Expected to finish: 2017-06-09
Last updated by the study team: 2019-01-23

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Patients who have had chemotherapy (other than sorafenib treatment), large field radiotherapy, or major surgery must wait 4 weeks prior to entering the study.
Patients may not be receiving any agents not approved by the Food and Drug Administration (FDA) within the past 4 weeks.
Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Proteinuria, as demonstrated by a 24-hour protein of greater than or equal to 2000 mg. Urine protein will be screened by urine protein-creatinine ratio (UPC). For UPC ratio greater than 1.0, a 24-hour urine protein will need to be obtained and the level should be less than 2000 mg for patient enrollment.
Uncontrolled intercurrent illness including, but not limited to, hypertension (systolic blood pressure (BP) greater than 140, diastolic BP greater than 90), ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
No anti-coagulation therapy is allowed with the exception of low-dose aspirin.
No bleeding diathesis.
Patients with a history of bleeding varices in previous 1 year are excluded (unless patient has subsequently had a liver transplant. Those with gastric varices or varices that are deemed as high risk by the endoscopist should be placed on appropriate medical therapy as advised by the gastroenterologist.
History of peptic ulcer disease or gastritis within 6 months of TRC105 administration, unless patient has received adequate treatment for peptic ulcer disease and has evidence of complete resolution documented by esophagogastroduodenoscopy (EGD). Mild gastritis is allowed.
Corrected QT interval (QTc) greater than 500 msec
Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy are excluded from this study due to the possibility of pharmacokinetic interactions between antiretroviral medications and sorafenib or TRC105. HIV positive patients not receiving antiretroviral therapy are excluded due to the possibility that sorafenib or TRC105 may worsen their condition and the likelihood that the underlying condition may obscure the attribution of adverse events with respect to sorafenib or TRC105.
History of hypersensitivity reaction to human or mouse antibody products
Patients with a history of familial bleeding disorders
Patients with a history of hereditary hemorrhagic telangiectasia (Osler-Weber- Rendu Syndrome).
Pregnancy and breast feeding are exclusion factors. Enrolled patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, the duration of study participation and 3 months after the end of the treatment.
Patients with unhealed wounds for more than 30 days.
INCLUSION OF WOMEN AND MINORITIES:
Men and women of all races and ethnic groups are eligible for this trial.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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