Bevacizumab and Erlotinib or Sorafenib as First-Line Therapy in Treating Patients With Advanced Liver Cancer
Condition: Liver Cancer
MeSH terms: Liver Neoplasms
Intervention: bevacizumab; erlotinib hydrochloride; sorafenib tosylate
Intervention description: Given IV; Given orally; Given orally
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Maximum age: 116 Years
Healthy volunteers: No
Keywords: adult primary hepatocellular carcinoma; advanced adult primary liver cancer; recurrent adult primary liver cancer

Summary:

      RATIONALE: 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 and sorafenib may stop
      the growth of tumor cells by blocking some of the enzymes needed for cell growth.
      Bevacizumab, erlotinib, and sorafenib may also stop the growth of tumor cells by blocking
      blood flow to the tumor. It is not yet known whether giving bevacizumab together with
      erlotinib is more effective than giving sorafenib in treating patients with liver cancer.

      PURPOSE: This randomized phase II trial is studying how well giving bevacizumab together with
      erlotinib works compared with sorafenib as first-line therapy in treating patients with
      advanced liver cancer.
    

Eligibility 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 1.1 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 ≤ 2.0 times ULN

          -  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)