TRC105 for Liver Cancer That Has Not Responded to Sorafenib
Condition: Hepatocellular Carcinoma; Hepatocellular Cancer; Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: TRC105
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: CD105; Monoclonal Antibody; Anti-Angiogenic; Chimeric; Apoptosis; Liver Cancer

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Patients must have histopathological confirmation of Hepatocellular Carcinoma (HCC) by
             the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering
             this study.

        Or

        histopathological confirmation of carcinoma in the setting of clinical and radiological
        characteristics which, together with the pathology, are highly suggestive of a diagnosis of
        HCC.

          -  Patients must have disease that is not amenable to potentially curative resection or
             ablative techniques. In addition, disease must not be amenable to transhepatic
             arterial chemoembolization (TACE). Patients may have had prior TACE and had disease
             progression following it. Patients must not be considered potential candidates for
             liver transplantation. This determination will be made after hepatobiliary surgical
             input at the NCI multidisciplinary conference.

          -  All patients enrolled will be required to have measurable disease.

          -  If liver cirrhosis is present, patient must have a Child-Pugh A classification.

          -  Patients must have progressed on or been intolerant of prior sorafenib therapy.

          -  Patients must with cirrhosis have had esophagogastric endoscopy within the previous 6
             months prior to study entry for the assessment of varices. If the patient has not had
             this done they must be willing to undergo this procedure prior to study entry.

          -  Age greater than or equal to 18 years

          -  Life expectancy of greater than 3 months.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Patients must have normal organ and marrow function as defined below:

               -  Absolute neutrophil count greater than or equal to 1,500/mcL

               -  Platelets greater than or equal to 60,000/mcL

               -  Total bilirubin less than or equal to 3 times upper normal limits

               -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or
                  equal to 10 times upper limit of normal

               -  Creatinine less than or equal to 1.5 times upper normal limits OR creatinine
                  clearance greater than or equal to 40 mL/min/1.73 m^2 for patients with
                  creatinine levels above institutional normal, as calculated by the Cockcroft
                  Gault formula.

          -  Patients must have recovered from any acute toxicity related to prior therapy,
             including surgery. Toxicity should be less than or equal to grade 1 or returned to
             baseline.

          -  Patients must not have other invasive malignancies within the past 3 years (with the
             exception of non-melanoma skin cancers, carcinoma in situ of the cervix and
             noninvasive bladder cancer).

          -  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.

          -  Patient must be able to understand and willing to sign a written informed consent
             document.

        EXCLUSION CRITERIA:

          -  Patients who have had chemotherapy, large field radiotherapy, or major surgery must
             wait 4 weeks prior to entering the study (2 weeks is sufficient for targeted systemic
             therapy provided toxicity has recovered to less than or equal to grade 1).

          -  Patients may not be receiving any anti-cancer 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 urine
             protein-to-creatinine (UPC) ratio > 1.0, a 24-hour urine protein will need to be
             obtained and the level should be < 2000 mg for patient enrollment.

          -  Uncontrolled intercurrent illness including, but not limited to, hypertension
             (systolic blood pressure (BP) 160, diastolic BP > 100), 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 hemorrhagic gastritis within 6 months of TRC105
             administration, unless patient has received adequate treatment for peptic ulcer
             disease or hemorrhagic gastritis and has evidence of complete resolution documented by
             esophagogastroduodenoscopy (EGD). Mild gastritis is allowed.

          -  Corrected QT interval (QTc) > 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 TRC105. HIV positive patients not receiving
             antiretroviral therapy are excluded due to the possibility that TRC105 may worsen
             their condition and the likelihood that the underlying condition may obscure the
             attribution of adverse events with respect to 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.

        INCLUSION OF WOMEN AND MINORITIES:

        -Men and women of all races and ethnic groups are eligible for this trial.