University of Southern California
USC Norris Comprehensive Cancer Center
If you are a patient, please contact Keck Medical Center of USC at 800-USC-CARE.

Trial 3L-09-3


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).

Type: Treatment
Phase: Phase II
Status: Closed to Accrual with Ongoing Follow-up
Treatments: Anti-Angiogenesis, Immunotherapy
Randomized: Yes
Defintions of terms and FAQ about clinical trials.
Trial Leaders/Researchers:  Anthony El-Khoueiry, M.D.
Other Trial Staff:  Ramona Lujan, R.N., Raluca Agafitei, Coordinator, Mary Ordaz, D.M., Taison Tran, D.M.

Staff may log in to see study documents.


You may participate in this study if:
 Requirement
1Patient must have biopsy-proven pathologically confirmed advanced hepatocellular carcinoma. Fibrolamellar HCC is not allowed. Patient with advanced hepatocellular carcinoma are defined as patients who are not candidates for curative surgical resection or loco-regional therapy. The basis for the determination that the patient is not eligible for surgical or local therapy must be documented by the investigator in the enrollment information.
2Patient must have signed and dated IRB approved informed consent and HIPAA authorization forms.
3Patient must have measurable disease. All patients must have at least one previously un-irradiated measurable lesion by CT or magnetic resonance imaging (MRI) scan of greater than or equal to 20 mm. Ultrasound cannot be used for assessing measureable disease. The following are not considered measurable lesions;:bone lesions, ascites, pleural effusions.
4Patient has an ECOG performance status of 0-2
5Patient has a Childs-Pugh status of A. Patient has a CLIP Score less than or equal to 5
6The following prior therapies are allowed provided the lesion(s) have progressed since treatment or there are additional measurable, untreated lesions to be assessed in this study: Surgery, local ablation, trans-arterial hepatic-artery embolization (TAE), trans-arterial chemoembolization (TACE). These prior therapies must have been completed greater than or equal to 28 days prior to study entry. Current, recent (within 4 weeks of the first dose in this study), or planned participation in an experimental drug study is not permitted.
7Organ Function a) Hematologic: • Absolute neutrophil count greater than or equal to 1500 • Platelet count greater than or equal to 75,000 • Hemoglobin greater than or equal to 9 b) Hepatic: • Transaminases: Up to 5 times (X) upper limit of normal (ULN) (CTC Grade 2) • Total bilirubin up to 2.0 X ULN • Serum albumin > 2.5 • PT less or equal to 1.8 times ULN. Patients who require full dose anticoagulation, who are otherwise eligible for this trial, are allowed to have an appropriately prolonged International Normalized Ratio (INR). Warfarin is not allowed due to potential for adverse drug interaction with erlotinib. Other means of anticoagulation are allowed. c) Renal: • Creatinine less than or equal to 2.0 OR Creatinine clearance greater than or equal to 45 mL/min.
8The patient must have well-controlled blood pressure, defined as systolic blood pressure <150mmHg and/or diastolic blood pressure <100 mmHg.
9Women of childbearing potential (WOCBP) must be using a reliable method of contraception (including oral contraceptive pills, intrauterine device, physical barrier methods) to avoid pregnancy throughout the study and for 12 weeks after discontinuation of treatment in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea greater than or equal to 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level > 35mIU/mL]. Negative pregnancy test in WOCBP is required within 3 days prior to initiation of treatment.


You may not participate in this study if:
1WOCBP and fertile men who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire treatment period and for up to 12 weeks after treatment discontinuation; using a prohibited contraceptive method.
2Women with a positive blood serum pregnancy test within the screening/enrollment period; women who are breastfeeding.
3Patients who have had prior systemic therapy for HCC.
4Active infection requiring parenteral therapy or known HIV or AIDS.
5Patients with known brain metastases. If clinical evidence suggests brain metastases, patient should complete a brain radiologic assessment.
6Uncontrolled or significant cardiovascular disease including: myocardial infarction within past 6 months; uncontrolled angina within past 6 months; Class II-IV New York Heart Association (NYHA) congestive heart failure; grade 3 cardiac valve dysfunction; cardiac arrhythmia not controlled by medication; history of stroke or transient ischemic attack within 6 months; history of arterial thrombotic event (ATE) of any type within the previous 6 months.
7Significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease) within 6 months.
8Evidence of decompensated liver disease as evidenced by: clinically significant ascites refractory to diuretic therapy; evidence of hepatic encephalopathy, coagulopathy not corrected by conservative measures.
9A history of CTC Grade 3 bleeding esophageal or gastric varices within the past 2 months. Prior variceal bleed is permitted if patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months. Patients at risk for varices (based on the following: known history of esophageal or gastric varices; evidence of hepatic cirrhosis and/or portal hypertension including biopsy-proven cirrhosis, hypersplenism, or radiographic findings of varices) will be screened (using either esophagogastroduodenoscopy [EGD] or capsule endoscopy) for esophageal varices. If varices are identified that require intervention (banding), patient will not be eligible until varices are adequately treated.
10Patient presenting with grade 2 or greater gastric varices will not be eligible for the study.
11History of hemoptysis (greater than or equal to ½ teaspoon of bright red blood per episode) within 1 month prior to registration.
12Evidence of bleeding diathesis or coagulopathy.
13Need for warfarin therapy due to potential for adverse drug interaction with erlotinib. Other means of anticoagulation are allowed.
14Uncontrolled intercurrent illness including but not limited to: a history of or current evidence of unexplained nephrotic syndrome; other severe illness/disease that would preclude study participation.
15Any prior history of hypertensive crisis or hypertensive encephalopathy.
16Inability to take or absorb oral medication.
17Proteinuria at screening as demonstrated by: urine for proteinuria greater than or equal to 2+ using urine dipstick. (patients discovered to have greater than or equal to 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate less than or equal to 1g of protein in 24 hours to be eligible).
18History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration.
19Serious, non-healing wound, active ulcer, or untreated bone fracture.
20Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, or anticipation of need for major surgical procedure during the course of the study.
21Minor surgical procedures, fine needle aspirations or core biopsies, excluding placement of a vascular access device, within 7 days prior to study registration.
22History of allergy to bevacizumab, erlotinib, sorafenib or related compounds.
23History of organ transplantation.
24Other primary malignancy within past 5 years except carcinoma in situ of the cervix or urinary bladder or non-melanoma skin cancer.
25Mental incapacitation or psychiatric illness that would preclude study participation.
26Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study.
27Age less than or equal to 18 years.
28Inability to comply with study and/or follow-up procedures.



For further information on a study, please contact the Clinical Investigation Support Office at (323) 865-0451, or clinical.trials@med.usc.edu.

To schedule a consultation with the hospital, please call our New Patient Referrals Office at (323) 865-3111.