A Phase II Study of TRC105 in Patients With Hepatocellular Carcinoma (HCC) Who Have Progressed on Sorafenib

Inclusion Criteria

- INCLUSION CRITERIA:

- Patients must have histopathological confirmation of Hepatocellular Carcinoma (HCC)
by the Laboratory of Pathology of the 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.

- 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

- AST/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 (or so-called targeted' systemic therapy), large
field radiotherapy, or major surgery must wait 4 weeks prior to entering the study.

- Patients may not be receiving any anti-cancer agents not approved by the 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 > 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 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 EGD. Mild gastritis is allowed.

- QTc > 500 msec.

- 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.