Doxorubicin and Bortezomib in Treating Patients With Liver Cancer

Inclusion Criteria:

• Patients must have microscopically confirmed hepatocellular carcinoma not amenable to curative resection; if patients have an isolated lesion in one lobe of the liver, a liver surgeon should determine resectability; central review is not required
• Patients must have measurable disease as determined by RECIST criteria, amenable to biopsy; patients are not mandated to allow biopsy, even though it is an important aspect of this clinical trial
• Patients with history of untreated malignancy other than HCC are not eligible
• Patients with history of malignancy treated within the past 5 years are not eligible; history of carcinoma-in-situ of cervix, squamous cell cancer of skin, basal cell cancer of skin, previously treated are allowed; others are excluded as recurrence of disease may confuse response rate and/or survival endpoints
• Patients must have ECOG performance status of 0-2
• Patients must not have had prior systemic chemotherapy for HCC; patients on antineoplastics for non-malignant diseases, such as methotrexate for rheumatoid arthritis, are allowed, providing patients have been off these agents for at least 4 weeks and all related toxicities have resolved to baseline
• Patients must not have had prior use of octreotide or tamoxifen as therapy for HCC
• Patients may have had prior embolization without chemotherapy; patients who have had chemoembolization are not eligible; patients may have had radiofrequency (RF) ablation, cryosurgery or ethanol injection; patients must have documented progression with the involved lesion or at least one previously untreated lesion amenable to biopsy
• Platelet count must be >= 100,000/mm^3 in absence of splenomegaly; platelet count must be >= 75,000/mm^3 with splenomegaly
• ANC must be >= 1,500/mm^3 in absence of splenomegaly; ANC must be =< 1,000/mm^3 with splenomegaly
• Alkaline phosphate must be =< 5 x institutional ULN
• AST must be =< 5 x institutional ULN
• Bilirubin must be =< 2 mg/dl
• Patients may not exhibit Child Pugh scale grade C cirrhosis
• Serum creatinine=< 2.0 mg/dl
• Patients must have no baseline peripheral neuropathy > grade 1
• Patients with known allergy to boron, mannitol or bortezomib are not eligible
• Women must not be pregnant or breast-feeding due to the uncertain effects of bortezomib in the developing fetus and young infants
• All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
• Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
• Patients must not have an underlying medical condition that precludes safe participation in this clinical trial
• Patients must not have psychiatric illness or continued substance abuse that may impair the ability to provide informed consent or prevent safe administration of bortezomib
• Patients must not have known bleeding diathesis, INR > 1.5 or PTT > 1.5 x institutional ULN (required due to biopsy portion of study); use of vitamin K or fresh frozen plasma to correct values just prior to biopsy or enrollment is not allowed
• Patients with EF < 50% measured by ECHO or MUGA are not eligible
• Patients on verapamil who cannot be switched to an alternative medication are not eligible (due to the interaction with doxorubicin)