Safety and Pharmacokinetics of Treating Liver Cancer With Drug-Eluting Beads

• Patients with pathologically proven hepatic-dominant metastases from abdominal or gastrointestinal tract primary malignancy or melanoma where the life limiting component of the disease is hepatic metastasis
• Patients must have unresectable hepatic lesions or must be unable or unwilling to undergo surgical resection. Patients may have undergone prior wedge resection of the liver for metastatic disease
• All patients must be refractory to or intolerant of approved standard systemic therapy.

Specifically:

• Patients with metastatic colorectal must have received 5-FU and leucovorin in combination with either oxaliplatin and/or irinotecan, since level 1 evidence support increase survival with these regimens, compared to 5-FU and leucovorin alone.

• Patients with melanoma must have received IL-2 or other immunotherapy options (such as ipilimumab or adoptive cell therapy) that have been reported to have efficacy.

  • Patients with extrahepatic metastases or an unresected primary lesion will be considered eligible if the extrahepatic disease is minimal
  • Extent of hepatic metastases is \<60% of total hepatic volume.
  • Patients must have at least one lesion that can be readily biopsied (at least 10mm diameter)
  • ECOG performance status less than or equal to 2
  • Life expectancy > 3 months
  • At least 18 years of age
  • Age \< 85 years
  • Patients must have had no chemotherapy, radiotherapy, or biologic therapy for their malignancy for at least 4 weeks (or until response can be adequately assessed) prior to treatment and must have recovered from all clinically significant side effects of therapeutic and diagnostic interventions. Anti-VEGF agents (eg, Avastin) may not be administered less than 4 weeks prior to DEB-TACE treatment.
  • Patients are not to receive conventional chemotherapy or therapeutic monoclonal antibodies while receiving protocol treatment
  • Hematology:
• Absolute neutrophil count greater than 1500/mm(3) without the support of Filgrastim.
• Platelet count greater than 75,000/mm(3).

• Hemoglobin greater than 8.0 g/dl.

  -Chemistry:

• Serum ALT/AST less than or equal to 3 times the upper limit of normal.
• Serum creatinine less than or equal to 2.0 mg/dl unless the measured creatinine clearance is greater than 60 mL/min
• Total bilirubin less than or equal to 2 mg/dl.
• INR \<1.5

• PTT less than or equal to 1.3 times control unless a mixing study confirms the presence of a lupus anticoagulant as the cause for the prolonged PTT.

  • Screening electrocardiogram is normal with QTc less than or equal to 480msec).

EXCLUSION CRITERIA:

• Significant cardiac or pulmonary insufficiency as evidenced by

  • history of congestive heart failure with an LVEF \< 40%
  • history of COPD or other chronic pulmonary disease with PFT s indicating an FEV1 less than 30% or a DLCO less than 40% predicted for age
• Portal Vein Occlusion or other contraindications to chemoembolization
• Inflammatory bowel disease
• Prior chemoembolization therapy
• Prior precutaneous hepatic perfusion therapy
• Prior selective internal radiation therapy (SIRT) with Yttrium-90
• Prior biliary diversion surgery
• Previous liver resection other than wedge resection.
• Pregnant patients and nursing mothers will be excluded because of the unknown effects of this therapy on the fetus or nursing infants.
• Patients taking immunosuppressive drugs or requiring ongoing chronic anticoagulation will not be eligible.
• Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy.
• Patients with severe allergic reactions to iodine contrast which cannot be controlled by premedication with antihistamines and steroids are not eligible as a hepatic angiogram is needed for this procedure.
• Patients with a known prior hypersensitivity reaction or other contraindication to irinotecan will be excluded.
• Patients taking phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, St. John s Wort, or other CYP3A inducers or inhibitors are not eligible for this study.
• Patients are prohibited from receiving other experimental agents/adjuvant treatments during the study.
• Patients with more than one active primary malignancy, except for basal cell carcinoma or superficial bladder neoplasia, are to be excluded.