Phase Ib Study of the Safety and Pharmacokinetics of Chemoembolization With Irinotecan-Eluting Beads for the Treatment of Hepatic Metastases

Inclusion Criteria

- INCLUSION CRITERIA:

- 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.