A Randomized Open-Label Multi-Institution Phase II Study of the Combination of Bevacizumab and Erlotinib Compared to Sorafenib in the First-Line Treatment of Patients With Advanced Hepatocellular Carcinoma (HCC)

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Pathologically confirmed advanced hepatocellular carcinoma (HCC)

- Childs-Pugh class A

- CLIP score ≤ 5

- Not a candidate for curative surgical resection or loco-regional therapy

- Measurable disease as per RECIST criteria, defined as ≥ 1 previously unirradiated,
bidimensionally measurable lesion ≥ 20 mm by CT scan or MRI (triphasic spiral CT scan
or MRI employing a "liver protocol" image capture technique required)

- Bone lesions, ascites, and pleural effusions are not considered measurable
lesions

- No fibrolamellar HCC

- No known brain metastases

- No prior organ transplantation

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 75,000/mm³

- Hemoglobin ≥ 9 g/dL

- Transaminases ≤ 5 times upper limit of normal (ULN)

- Total bilirubin ≤ 3.0 times ULN

- Serum albumin > 2.5 g/dL

- PT ≤ 1.8 times ULN

- Prolonged INR allowed for patients who require full dose anticoagulation

- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 45 mL/min

- Urine protein < 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine
collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 weeks after
completion of study treatment

- Able to take and absorb oral medication

- No active infection requiring parenteral therapy

- No known HIV or AIDS

- No uncontrolled blood pressure (BP), defined as systolic BP ≥ 150 mm Hg and/or
diastolic BP ≥ 100 mm Hg

- No uncontrolled or significant cardiovascular disease, including any of the
following:

- Myocardial infarction within the past 6 months

- Uncontrolled angina within the past 6 months

- New York Heart Association class II-IV congestive heart failure

- Grade 3 cardiac valve dysfunction

- Cardiac arrhythmia not controlled by medication

- Stroke or transient ischemic attack within the past 6 months

- Arterial thrombotic event of any type within the past 6 months

- No significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic
dissection, or peripheral vascular disease) within the past 6 months

- No decompensated liver disease as evidenced by clinically significant ascites
refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy not corrected
by conservative measures

- No grade 3 bleeding esophageal or gastric varices within the past 2 months

- Prior variceal bleeding allowed provided patient has undergone banding or
sclerotherapy and there has been no evidence of bleeding for 2 months

- No gastric varices ≥ grade 2

- No hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per episode) within the past
month

- No evidence of bleeding diathesis or coagulopathy

- No concurrent uncontrolled illness, including, but not limited to, a history of or
current evidence of unexplained nephrotic syndrome or other severe illness/disease
that would preclude study participation

- No history of hypertensive crisis or hypertensive encephalopathy

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No serious, non-healing wound, active ulcer, or untreated bone fracture

- No significant traumatic injury within the past 28 days

- No history of allergy to bevacizumab, erlotinib hydrochloride, sorafenib tosylate, or
related compounds

- No other primary malignancy within the past 5 years, except carcinoma in situ of the
cervix or urinary bladder or nonmelanoma skin cancer

- No mental incapacitation or psychiatric illness that would preclude study
participation

- Not incarcerated or compulsorily detained (i.e., involuntarily incarcerated) for
treatment of either a psychiatric or physical illness (e.g., infectious disease)

PRIOR CONCURRENT THERAPY:

- Prior surgery, local ablation, trans-arterial hepatic artery embolization, or
trans-arterial chemoembolization are allowed provided the lesion(s) have progressed
since treatment OR there are additional measurable, untreated lesions present

- No prior systemic therapy for HCC

- No prior organ transplantation

- More than 7 days since prior minor surgical procedures, fine needle aspirations, or
core biopsies (excluding placement of a vascular access device)

- More than 28 days since any prior therapy

- More than 28 days since prior and no concurrent major surgical procedure or open
biopsy

- More than 28 days since prior and no concurrent participation in another experimental
drug study

- No other concurrent anticancer or antitumor therapy, including chemotherapy,
radiotherapy, immunotherapy, or hormonal anticancer therapy

- No other concurrent investigational agents

- No concurrent warfarin (other types of anticoagulation allowed)