| Criteria: |
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Inclusion Criteria:
- The patient has histologically or cytologically confirmed, unresectable HCC.
- The patient has at least one target lesion measurable according to Response
Evaluation Criteria in Solid Tumors (RECIST) guidelines. Target lesion(s) must not
lay within a previously irradiated, ablated, or chemoembolized area. If a lesion
does lie in such an area, there must be evidence of growth on successive imaging
studies, including tumor hypervascularity, in order for such a lesion to be
considered a target lesion.
- The patient has not received prior systemic therapy for HCC. Patients may have
received prior embolization, chemoembolization, intra-arterial chemotherapy infusion,
ethanol injection, radiofrequency ablation, or cryosurgery.
- The patient has a life expectancy of ≥ 12 weeks.
- The patient has resolution to Grade ≤ 1 by the National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0, of all clinically
significant adverse events.
- The patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) of
0-1.
- The patient has a Child-Pugh Classification score of A or B.
- The patient has adequate hematologic function as defined by absolute neutrophil count
(ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9 g/dL, and platelets ≥ 75 x 109/L.
- The patient has adequate hepatic function as defined by a total bilirubin ≤ 3.0 mg/dL
and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 5 x the upper limit
of normal (ULN).
- The patient has adequate renal function as defined by serum creatinine ≤ 1.5 x the
institutional ULN or calculated creatinine clearance (per the Cockcroft-Gault
formula) > 50 mL/minute.
- The patient has fasting serum glucose < 160 mg/dL or below the ULN and/or hemoglobin
A1C < 7%. If baseline nonfasting glucose < 160 mg/dL, fasting glucose measurement is
not required.
- The patient must have adequate coagulation function as defined by International
Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) < 1.5 x the ULN.
- If a female of childbearing potential, the patient has a negative serum pregnancy
test performed within 7 days prior to first administration of study therapy, and
agrees to use adequate contraception (hormonal or barrier method of birth control;
abstinence) for the duration of study participation.
- The patient has the ability to understand and the willingness to sign a written
informed consent document.
Exclusion Criteria:
- The patient has brain metastases.
- The patient has leptomeningeal disease.
- The patient has received prior systemic chemotherapy, biologic or antiangiogenic, or
other systemic anticancer treatment for HCC.
- The patient has received chemoembolization, irradiation, or other locoregional
therapy for HCC within 28 days of first dose of study therapy.
- The patient has received chemoembolization, irradiation, or other locoregional
therapy for HCC within 28 days of first dose of study therapy.
- The patient has ascites or encephalopathy uncontrollable by medical management.
- The patient has experienced esophageal or gastric variceal bleeding within the 6
months prior to first dose of study therapy.
- The patient has acute hepatitis.
- The patient has fibrolamellar HCC.
- The patient is receiving any other investigational agent(s).
- The patient has a history of treatment with other agents targeting the IGF receptor.
- The patient has a history of allergic reactions attributed to compounds of chemical
or biologic composition similar to those of IMC-A12 or sorafenib.
- The patient has poorly controlled diabetes mellitus. Patients with a history of
diabetes mellitus are allowed to participate, provided that their blood glucose is
within normal range and that they are on a stable dietary or therapeutic regimen for
this condition.
- The patient is positive for infection with the human immunodeficiency virus.
- The patient has an uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection requiring parenteral antibiotics, or a psychiatric
illness/social situations that would limit compliance with study.
- The patient has congestive heart failure > class II NYHA, unstable angina pectoris,
new onset of angina pectoris, myocardial infarction within the past 6 months, or
cardiac ventricular arrhythmias requiring antiarrhythmic therapy.
- The patient has uncontrolled hypertension despite optimal therapy.
- The patient has experienced thrombotic or embolic events, including transient
ischemic attacks, within 6 months prior to study entry.
- The patient has experienced a hemorrhage or bleeding event ≥ NCI-CTCAE Grade 3 within
4 weeks prior first dose of study therapy.
- The patient has a serious nonhealing wound, ulcer, or bone fracture.
- There is evidence or history of bleeding diathesis or coagulopathy.
- The patient is receiving therapeutic anticoagulation with Vitamin K antagonists such
as warfarin or phenprocoumon, or with heparins or heparinoids. Low dose
warfarin/phenprocoumon is permitted if the INR is < 1.5. Low dose aspirin (300
mg/day) is permitted.
- The patient is receiving CYP 3A4 inducers (such as rifampicin, St. John's Wort,
phenytoin, phenobarbital or dexamethasone).
- The patient is unable to swallow the sorafenib tablets.
- The patient is pregnant or lactating.
- The patient has a history of another primary cancer, with the exception of: a)
curatively resected nonmelanomatous skin cancer; b) curatively treated cervical
carcinoma in situ; or c) other primary solid tumor treated with curative intent and
no known active disease present and no treatment administered during the last 3
years. |