Chemoembolization and Bevacizumab in Treating Patients With Liver Cancer That Cannot Be Removed With Surgery
Condition: Liver Cancer
MeSH terms: Liver Neoplasms
Intervention: bevacizumab
Intervention description: Given IV, 10mg/kg evey two weeks starting 1 week prior to the first chemoembolization.
Patients crossed over to the Bevacizumab arm will receive Bevacizumab after week 14 at the same dose.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma

Summary:

      RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, cisplatin, and
      mitomycin, work in different ways to stop the growth of cancer cells, either by killing the
      cells or by stopping the cells from dividing. Chemoembolization kills tumor cells by blocking
      the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Monoclonal
      antibodies, such as bevacizumab, can kill any tumor cells that are left after
      chemoembolization by blocking their ability to grow and spread.

      PURPOSE: This randomized phase II trial is studying to see if chemoembolization followed by
      bevacizumab works better than chemoembolization alone in treating patients who have liver
      cancer that cannot be removed with surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age > 18 year old

          -  Histologically or cytologically documented HCC

          -  Patients must have bi-dimensional measurable disease by CT or MRI scan that does not
             exceed 50% of the liver parenchyma

          -  Patients must be considered clinical candidates for chemoembolization, with at least
             one lesion > 3cm and no lesion > 15cm in its longest diameter

          -  Patients awaiting cadaveric orthotopic liver transplantation are eligible if they meet
             all other criteria. These patients must have a model for end-stage liver disease
             priority score < 28 points at entry

          -  Cirrhosis Child-Pugh class A or B

          -  Patients with documented grad III varices or prior history of UGI bleeding will
             require endoscopic evaluation prior to treatment under this protocol.

          -  Platelet count equal or greater than 60,000/μL

          -  Female patients must use effective contraception, be surgically sterile or be
             postmenopausal; male patients must be using barrier contraception or be surgically
             sterile

          -  Patients must be willing and able to comply with all study requirements and have
             signed the informed consent

        Exclusion Criteria:

          -  Previous history of liver transplantation

          -  Fibrolamellar histology

          -  Prior antiangiogenesis therapy

          -  Presence of extrahepatic disease

          -  Presence of biliary obstruction defined as biliary dilatation and total bilirubin >
             2.5mg/dl

          -  Thrombosis of the main portal vein

          -  Absolute contraindications to doxorubicin, mitomycin-C, cisplatin, iodinated contrast
             material, Avitene or dexamethasone treatment

          -  Other active malignancies during the past year (except for non-melanoma skin cancer or
             in situ carcinomas)

          -  ECOG PS> 2 or life expectancy < 12 weeks

          -  History or evidence upon physical examination of CNS disease

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to Day 0, or anticipation of need for major surgical procedure within 3 months
             of study entry; fine needle aspirations within 7 days prior to Day 0

          -  Current or recent (within the 10 days prior to Day 0) use of full-dose oral or
             parenteral anticoagulants (except as required to maintain patency of preexisting,
             permanent indwelling IV catheters) or thrombolytic agent (for subjects receiving
             warfarin, international normalized ration of < 1.5)

          -  Chronic, daily treatment with aspirin (> 325mg/day) or nonsteroidal anti-inflammatory
             medications

          -  Positive pregnancy test or lactation

          -  Proteinuria at baseline or clinically significant impairment of renal function.
             Subjects unexpectedly discovered to have > 1+ proteinuria at baseline should undergo a
             24-hour urine collection, which must be an adequate collection and must demonstrate <
             500 mg of protein/24 hr to allow participation in the study

          -  Serious, nonhealing wound, ulcer, or bone fracture

          -  Evidence of bleeding diathesis or coagulopathy

          -  Current or recent (within the 28 days prior to Day 0) participation in another
             experimental drug study

          -  Clinically significant cardiovascular disease, New York Heart Association Grade II or
             greater congestive heart failure, serious cardiac arrhythmia requiring medication, or
             Grade II or greater peripheral vascular disease within 1 year prior to Day 0

          -  Prior history of hypertensive crisis of hypertensive encephalopathy

          -  History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             Day 1

          -  History of hemoptysis within 1 month prior to Day 1

          -  Significant vascular disease within 6 months prior to Day 1

          -  Screening clinical laboratory values:

               -  ANC of < 1500/μL

               -  INR of > 1.5

               -  Total bilirubin of > 2.5mg/dL

               -  AST or ALT > 5 times upper limit of normal

               -  Serum creatinine of > 2.0 mg/dL or creatinine clearance < 45 mL/min

               -  Hemoglobin of < 8.5 gm/dL

          -  History of other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates use of an investigational drug or that might affect interpretation of
             the results of the study or render the subject at high risk from treatment
             complications