Bevacizumab and Erlotinib in Inoperable and Metastatic Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Bevacizumab; Erlotinib
Intervention description: 15 mg/KG I.V. every 21 days; 150 mg orally every day
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Inoperable and Metastatic Hepatocellular Carcinoma

Summary:

      The primary efficacy endpoint will be the proportion of subjects that remain free of
      progression at the 27th week following the onset of treatment. Secondary objectives include
      the subject's time in weeks from treatment onset to documented disease progression as
      assessed by the RECIST criteria, response rate, median and overall survival, safety and
      tolerability.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects should have histologically or cytologically confirmed diagnosis of
             hepatocellular carcinoma, regardless of biopsy site.

          -  Subjects with a liver mass and markedly elevated AFP (>500ng/mL) are eligible.

          -  Subjects should not be on the liver transplantation schedule

          -  Subjects can have prior therapy with sorafenib (nexavar) only if the therapy was
             stopped due to toxicity or allergic reaction soon after starting. Subjects must have
             been treated for less than two weeks to be eligible.

          -  Radiation therapy for palliation to the areas outside the site of tumor used for
             measurements is permitted. If a subject has received radiation therapy to the liver,
             the subject id eligible if there is a new lesion or if the prior lesion has increased
             in size.

          -  Subjects who have recovered from prior surgical procedure

          -  Performance status of ECOG 0-2

          -  Measurable or evaluable disease

          -  Be declared unresectable or not suitable candidates for surgery

          -  Adequate organ functions

          -  Serum bilirubin <3 mg/dl, AST <5x ULN, ALT <5XULN

          -  Serum albumin >2.5 g/dl

          -  Serum creatinine < 2.0 mg/dl

          -  ANC >1200 MM3

          -  Platelet count >75,000/ml

          -  PT/INR < 1.5 X ULN

          -  Life expectancy of >3 months

          -  Subjects should be able to sign informed consent and be agreeing to comply with
             therapy and follow up.

          -  Negative pregnancy test in women with childbearing potential, within one week prior to
             initiation of treatment.

          -  Fertile men and women must agree to use adequate contraception prior to study entry,
             for the duration of study participation, and for at least 1 week after therapy.

          -  Age >/= 18 years. The agents Bevacizumab and Erlotinib have not been studied in
             pediatric subjects, thus the doses to be used in this study cannot be assumed to be
             safe in children.

        Exclusion Criteria:

          -  Surgically resectable disease

          -  Subjects with active bacterial infections

          -  Subjects with brain metastases

          -  Pregnant women (positive pregnancy test) or lactating

          -  No other malignancy is allowed except for adequately treated basal cell (or squamous
             cell) skin cancer, in situ cervical cancer or other cancer for which the subject has
             been disease-free for five years.

          -  Abnormalities of the cornea based on history (e.g. dry eye syndrome, Sjogren's
             syndrome) or congenital abnormality (e.g. Fuch's dystrophy).

          -  Current, recent (within 4 weeks of the first infusion of the study), or planned
             participation in an experimental drug study other than a Genentech-sponsored
             Bevacizumab/Erlotinib cancer study

          -  Hepatic encephelopathy (as per treating physician's evaluation)

          -  Uncontrolled blood Pressure >150/100 mmHg

          -  Unstable angina

          -  NYHA grade II or greater congestive heart failure

          -  History or myocardial infraction within 6 months

          -  History of stroke within 6 months

          -  Clinically significant peripheral vascular disease (clinically significant venous or
             arterial thrombotic disease).

          -  Evidence of bleeding diathesis or coagulopathy

          -  Urine protein: creatinine ratio >1.0 at screening

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to Day 0

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Inability to comply with study and/or follow-up procedures

          -  Gastrointestinal disease resulting in an inability to take oral medication or a
             requirement for intravenous hyperalimentation.

          -  History of significant gastrointestinal bleeding requiring procedural intervention
             (e.g. variceal banding, TIPS procedure, arterial embolization, topical coagulation
             therapy) within six months prior to study Day 0.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0, or anticipation of need for major surgical procedure during the course
             of the study.

          -  Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
             prior to Day 0