Bevacizumab and Erlotinib in Treating Patients With Advanced Liver Cancer
Condition: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer
MeSH terms: Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: bevacizumab; erlotinib hydrochloride
Intervention description: Given IV, 10 mg/kg, days 1 and 15 in every cycle; Given orally, 150 mg, every day during each cycle.
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Erlotinib Hydrochloride; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving bevacizumab together with erlotinib works in
      treating patients with advanced liver cancer. Monoclonal antibodies, such as bevacizumab, can
      block tumor growth in different ways. Some block the ability of tumor cells to grow and
      spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
      Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Bevacizumab and erlotinib may also stop the growth of tumor cells by blocking blood
      flow to the tumor. Giving bevacizumab together with erlotinib may kill more tumor cells
    

Eligibility criteria:

        Inclusion Criteria:

          -  Absolute neutrophil count >= 1,500/mm^3

          -  Creatinine =< 2 mg/dL

          -  Albumin >= 2.5 g/dL

          -  Total bilirubin =< upper limit of normal (ULN)

          -  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN

          -  Alkaline phosphatase =< 5 times ULN

          -  Urine protein:creatinine ratio < 1.0 OR 24-hour urine protein < 1,000 mg

          -  Not pregnant or nursing:

        No nursing for >= 6 months after completion of study treatment

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during study and for >= 6 months
             after completion of study treatment

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to bevacizumab or erlotinib hydrochloride

          -  No abnormalities of the cornea, including any of the following:

        History of dry eye syndrome or Sjögren's syndrome; Congenital abnormality (e.g., Fuch's
        dystrophy); Abnormal slit-lamp examination using a vital dye (e.g., fluorescein,
        Bengal-Rose); Abnormal corneal sensitivity test (e.g., Schirmer test or similar tear
        production test)

          -  No stroke or transient ischemic attack within the past 6 months

          -  No uncontrolled high blood pressure, history of labile hypertension, or history of
             poor compliance with an antihypertensive regimen

          -  No unstable angina pectoris within the past 6 months

          -  No symptomatic congestive heart failure

          -  No myocardial infarction within the past 6 months

          -  No serious uncontrolled cardiac arrhythmias

          -  No uncontrolled diabetes mellitus

          -  No active or uncontrolled infection

          -  No impaired GI function or disease that may significantly alter the absorption of
             erlotinib hydrochloride (e.g., ulcerative disease, uncontrolled nausea, vomiting, or
             diarrhea, malabsorption syndrome, or bowel obstruction)

          -  Able to swallow tablets

          -  No psychiatric illness or social situation that would limit compliance with study
             requirements

          -  No history of nephrotic-range protein

          -  No history of bleeding diathesis

          -  No encephalopathy

          -  No serious nonhealing wounds, skin ulcers, or bone fractures

          -  No clinically significant peripheral vascular disease

          -  No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
             human antibodies

          -  No history of a GI bleed that required procedural intervention (e.g., variceal
             banding, surgical shunt, transvenous intrahepatic porto-systemic shunt [TIPS]) within
             the past 3 months

          -  No significant traumatic injury within the past 28 days

          -  No other prior malignancy within the past 5 years except for the following:

        Adequately treated basal cell or squamous cell skin cancer; Adequately treated in situ
        cervical cancer; Stage I or II cancer from which the patient is currently in complete
        remission; Stage I chronic lymphocytic leukemia

          -  Recovered from all therapy-related toxicities

          -  No more than 1 prior systemic or liver directed drug therapy including transarterial
             chemoembolization (TACE) (multiple TACEs will count as 1 prior regimen irrespective of
             their total numbers) that were used for HCC

          -  No chemotherapy for HCC within the past 4 weeks (6 weeks for nitrosoureas or mitomycin
             C)

          -  No biological therapy or immunotherapy for HCC within the past 4 weeks

          -  Prior surgery, regional therapy (e.g., transarterial embolization), liver
             transplantation, or other liver-directed ablative therapies of discrete lesions
             allowed provided any related progressive or recurrent disease is documented

          -  No cryotherapy, radiofrequency ablation, ethanol injection, or photodynamic therapy
             within the past 6 weeks:

        Indicator lesions must be outside the area of prior treatment OR if the lesion is inside
        the area of prior treatment, there must be clear evidence of disease progression associated
        with that lesion

          -  No core biopsy within the past 7 days

          -  No radiotherapy within the past 4 weeks

          -  No prior antiangiogenesis agent or antiepidermal growth factor receptor drug

          -  No prior treatment with hepatic arterial infusion with chemotherapy or yttrium Y
             90-labeled microspheres

          -  No other concurrent investigational agents

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No other concurrent anticancer therapy

          -  Concurrent full-dose anticoagulants (e.g., warfarin) with international normalized
             ratio (INR) > 1.2 allowed provided the following criteria are met:

        An in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant (or on a
        stable dose of low molecular weight heparin)

          -  AND (continued from above) No active bleeding or pathological condition that carries a
             high risk of bleeding (e.g., tumor involving major vessels, gastrointestinal [GI]
             ulceration, or known varices)

          -  No concurrent major surgical procedures

          -  Histologically confirmed hepatocellular carcinoma (HCC):

               -  No fibrolamellar subtype HCC

               -  Advanced disease

          -  Not a candidate for surgical resection or liver transplantation

          -  Measurable disease:

               -  Edges of the indicator lesion must be clearly distinct on CT scan

               -  Lesions that measure at least 1 cm but less than 2 cm only must use spiral CT
                  imaging for both pre- and post-treatment tumor assessments

          -  Child's Pugh classification A or B

          -  No primary brain tumor, brain metastasis, or other central nervous system (CNS)
             diseases

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Platelet count >= 75,000/mm^3

          -  No major surgery (e.g., laparotomy), open biopsy, or minor surgery (e.g., insertion of
             a vascular access device) within the past 4 weeks

          -  No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
             lung

          -  No abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28
             days

          -  No concurrent prophylactic hematopoietic colony-stimulating factors