Doxorubicin and Bortezomib in Treating Patients With 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; Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: doxorubicin; bortezomib
Intervention description: Given IV; Given IV
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: doxorubicin; doxorubicin hydrochloride; bortezomib; hepatocellular carcinoma

Summary:

      This phase II trial is studying how well giving doxorubicin together with bortezomib works in
      treating patients with liver cancer. Drugs used in chemotherapy, such as doxorubicin, work in
      different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may
      stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving
      doxorubicin together with bortezomib may kill more tumor cells.
    

Eligibility criteria:

        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 Response Evaluation Criteria In
             Solid Tumors (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 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 Eastern Cooperative Oncology Group (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 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

          -  Absolute neutrophil count (ANC) must be >= 1,500/mm^3 in absence of splenomegaly; ANC
             must be =< 1,000/mm^3 with splenomegaly

          -  Alkaline phosphate (ALT) must be =< 5 x institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (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

          -  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 known bleeding diathesis, international normalized ratio (INR)
             > 1.5 or Partial thromboplastin time (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 are not eligible

        Exclusion criteria:

          -  Patients have baseline peripheral neuropathy > grade 1

          -  Patients with history of untreated malignancy other than HCC

          -  Patients have had prior use of octreotide or tamoxifen as therapy for HCC

          -  Patients with known allergy to boron, mannitol or bortezomib

          -  Women are pregnant or breast-feeding (due to the uncertain effects of bortezomib in
             the developing fetus and young infants)

          -  Patients have an underlying medical condition that precludes safe participation in
             this clinical trial

          -  Patients have psychiatric illness or continued substance abuse that may impair the
             ability to provide informed consent or prevent safe administration of bortezomib

          -  Patients with ejection fraction (EF) < 50% measured by Echocardiography (ECHO) or
             Multiple gated acquisition (MUGA)

          -  Patients on verapamil who cannot be switched to an alternative medication (due to the
             interaction with doxorubicin)