Chemoembolization Versus Radioembolization in Treating Patients With Liver Cancer That Cannot Be Treated With Radiofrequency Ablation Or Surgery
Condition: Liver Cancer
MeSH terms: Liver Neoplasms
Intervention: yttrium Y 90 glass microspheres; Doxorubicin
Intervention description: Patients undergo radioembolization.; 75mg fixed dose
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: advanced adult primary liver cancer; localized unresectable adult primary liver cancer; recurrent adult primary liver cancer; adult primary hepatocellular carcinoma

Summary:

      RATIONALE: Chemoembolization kills tumor cells by blocking the blood flow to the tumor and
      keeping chemotherapy drugs near the tumor. Radioembolization kills tumor cells by blocking
      the blood flow to the tumor and keeping radioactive substances near the tumor. It is not yet
      known which treatment regimen is more effective in treating patients with liver cancer.

      PURPOSE: This randomized phase II trial is studying radioembolization to see how well it
      works compared with chemoembolization in treating patients with liver cancer that cannot be
      treated with Radiofrequency Ablation or removed by surgery.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Hepatocellular Carcinoma confined to the liver that is unresectable with surgery or
             unable to be treated with radiofrequency ablation diagnosed by biopsy or imaging
             criteria (CT/MRI)

          -  No segmental, lobar, or main portal vein thrombosis as evidenced by CT or MRI imaging

        Inclusion Criteria

          -  Adults > 18 years old of either gender

          -  Diagnosis of liver confined HCC confirmed by histology or American Association for the
             Study of Liver Diseases (AASLD) guidelines [59,60] [appendix A].

          -  Lesions < 1 cm in diameter have a low likelihood of being malignant and should be
             followed. Lack of growth over 1-2 years suggests it is not HCC.

          -  AFP >200 and radiological evidence (arterial hypervascularity) of lesion > 2 cm does
             not require biopsy.

          -  Two imaging modalities (triphasic CT, MRI, ultrasound, angiography) demonstrating
             "arterial hypervascularity" in the background of cirrhosis does not require biopsy

          -  One imaging modality with a lesion with arterial hypervascularity with wash out in
             early or delayed venous phase, does not require a biopsy

          -  Atypical appearances on imaging requires a biopsy.

          -  Non-conclusive biopsy requires closer monitoring

          -  For non-cirrhotics (by biopsy or imaging findings), diagnosis of HCC requires biopsy

          -  Patients with <50% liver involvement

          -  Measurable liver confined disease with bi-dimensional measurements, required within 4
             weeks of screening. Lesions reported on imaging as "too small to characterize",
             abdominal lymph nodes < 2.0 cm or ascites in the setting of cirrhosis are not
             considered metastatic disease unless cytology proven.

          -  No segmental, lobar or main portal vein thrombosis as evidence by cross sectional
             imaging

          -  Prior resection permitted, no prior systemic, ablative or infusion therapy permitted

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 [appendix B]

          -  Childs score of A or B [appendix C]

          -  Required lab parameters within 28 days of screening

          -  Serum bilirubin ≤ 2.0 mg/dl (unless segmental infusion can be performed

          -  AST and ALT ≤ 5 times upper limit of normal (ULN)

          -  Creatinine ≤ 1.5 times ULN

          -  Prothrombin time (PT)/ International normalized ratio (INR) ≤ 2.3 or PT ≤ 6 seconds
             above control. If subjects are being anticoagulated they can participate if proof of
             no coagulation abnormality existed prior to use of anticoagulants

          -  Negative serum or urine pregnancy test for females of child bearing potential

          -  Ability to understand and sign the informed consent; patient must have signed informed
             consent prior to registration on study

          -  Women of childbearing potential and sexually active males must use contraception while
             on study

          -  Lesions must be treatable angiographically by either radioembolization or
             chemoembolization.

        Exclusion criteria

          -  Cardiac disease: Congestive heart failure > class II New York Heart Association
             (NYHA). Patients must not have unstable angina (angina symptoms at rest) or new onset
             angina (began within the last 3 months) or myocardial infarction within the past 6
             months.

          -  Patients with infiltrative HCC are not eligible.

          -  Patients with bulk disease (≥70% tumor replacement of liver) are not eligible.

          -  Patients with ≥50% tumor replacement of liver, with an albumin < 3.0 g/dl are not
             eligible.

          -  Major surgery within 4 weeks prior to the screening visit

          -  Active clinically serious infection > Common Toxicity Criteria for Adverse Events
             (CTCAE v 4.0) Grade 2

          -  Any condition (psychological, physical or use/abuse of substances) which, in the
             opinion of the principal investigator (PI) or a sub-investigator (sub-I), would
             possibly endanger the subject during their participation in the study, or allow for
             non-compliance with the investigational drug and treatment under study.

          -  Due to the experimental nature of the therapy and the unknown risk to a fetus,
             pregnant and/or lactating women are not eligible to participate in this study.

          -  In the opinion of the investigator, patient is not a candidate/lesion not amenable for
             RFA (e.g. lesion location, shape, abnormal coagulation parameters, multi-focality).