Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy of Liver Metastasis From Colon Cancer With Systemic FOLFOX6

This is a multicentre, open labeled, prospective, randomized, controlled phase I/II study
designed to assess the clinical performance of chemoembolization with LC Bead, loaded with
irinotecan in combination with intravenous chemotherapy and bevacizumab versus intravenous
chemotherapy in combination with bevacizumab in the treatment of unresectable liver
metastases in patients with colorectal cancer.

Inclusion:

- Patients over 18 years of age, of any race or sex, who have histologic or radiologic
proof of colorectal cancer to the liver, who are able to give informed consent, will
be eligible.

- Patients with at least one measurable liver metastases, with size > 1cm (modified
RECIST criteria)

- Patients with liver dominant disease defined as ≥80% tumor body burden confined to the
liver

- Patients with patent main portal vein

- ECOG Performance Status score of < 2

- Life expectancy of > 3 months

- Non-pregnant with an acceptable contraception in premenopausal women.

- Hematologic function: ANC ≥ 1.5 x 109/L, platelets ≥75 x109/L, INR ≤1.3* (*If patient
is on anticoagulants, they must be able to stop medication temporarily prior to TACE
and must have INR ≤1.3 prior to receiving TACE) Adequate liver function as measured
by: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times ULN, albumin ≥2.5g/dl, Adequate
Hemoglobin and Hematocrit as measured by (Male: for approximate 45 - 62%; and
approximate Female: 37 - 48%) or Hemoglobin (Male: approximate 13 - 18 gm/dL Female:
approximate 12 - 16 gm/dL). If patient is asymptomatic with Hemoglobin for male 10 to
12.9 or Female 9.5 to 11.9 and do not wish to be transfused they still will be
eligible for treatment.

- Adequate renal function (creatinine ≤ 2.0mg/dl)

- Women of child bearing potential and fertile men are required to use effective
contraception (negative serum βHCG for women of child-bearing age)

- Signed, written informed consent

- Patient is at least one month out from any treatment for Stage III colorectal cancer

- Patient is at least one year out from any treatment for their Stage IV colorectal
cancer.

- these patients should not be candidates for curative treatments, and will have
recovered from any chemotherapeutic toxicities' they may have experienced."

- Less than 60% liver tumor replacement

Exclusion:

- "Any patient eligible for curative treatment (i.e. resection or radiofrequency
ablation). Note: resectability is defined as a single tumor <5cm with adequate liver
function defined: Total bilirubin ≤ 2.0mg/dl" non-resectability includes patients with
greater than 6, tumors close to blood vessels, patients with hepatic-pulmonary
shunting, or patients of poor performance"

- Active bacterial, viral or fungal infection within 72 hours of study entry

- Women who are pregnant or breast feeding

- Allergy to contrast media that cannot be managed with standard care (e.g. steroids),
making magnetic resonance imaging (MRI) or computed tomography (CT) contraindicated.

- Presence of another malignancy with the exception of cervical carcinoma in situ and
stage I basal or squamous carcinoma of the skin.

- Any contraindication for hepatic embolization procedures:

- Large shunt as determined by the investigator (pretesting with TcMMA not
required)

- Severe atheromatosis

- Hepatofugal blood flow

- Main portal vein occlusion (e.g. thrombus or tumor)

- Other significant medical or surgical condition, or any medication or treatment, that
would place the patient at undue risk and that would preclude the safe use of
chemoembolization or would interfere with study participation

- Patients with prior contraindications for the use of irinotecan therapy-this would
include chronic inflammatory bowel disease and or bowel obstruction, history of severe
hypersensitivity reactions to irinotecan hypochloride, trihydrate, lactic acid or to
any of the excipients of Camptostar, severe bone marrow failure, history of Gilbert
Syndrome or concomitant use with St. John's Wort

- Patients with prior contraindications for the use of fluorouracil, oxaliplatin,
leucovorin or bevacizumab