Hepatic Artery Infusion Pump Chemotherapy With Floxuridine and Dexamethasone in Combination With Systemic Chemotherapy for Patients With Colorectal Cancer Metastatic to the Liver

Background:

- Nearly 60% of patients with colorectal cancers will develop liver metastases over the
course of their disease.

- Of patients with metastatic colorectal cancer, the liver will be the sole site of
recurrence or the survival-limiting site of disease for 20%.

- Liver directed therapy, which has taken many forms over the last several decades, is a
potential means to prolong survival for properly selected patients and delay progression
at that site.

- Hepatic artery infusion of floxuridine (FUDR) via an implantable hepatic artery infusion
pump (HAIP) induces objective clinical response rates of nearly 50% in heavily
pretreated patients with metastatic colorectal cancer to the liver.

- The identification of patients likely to respond to HAIP and those likely to suffer
pumprelated adverse events is currently unknown, and has limited the wide-spread
adoption of this otherwise well tolerated intervention.

Objective:

- Determine the response rate in patients with unresectable metastatic colorectal cancer
treated with HAIP chemotherapy as measured by RECIST.

Eligibility:

- Histologically or cytologically confirmed colorectal adenocarcinoma metastatic to the
liver.

- Patients with liver metastases not amenable to resection to No Evidence of Disease (NED)
in one stage.

- Patients must have received systemic chemotherapy.

- Age greater than or equal to 18 years.

Design:

- Single arm, phase II study of HAIP chemotherapy.

- INCLUSION CRITERIA:

- Patients must have histologically or cytologically confirmed diagnosis of colorectal
adenocarcinoma, confirmed by the Laboratory of Pathology, NCI.

- Patients must have measurable liver metastatic disease.

- Patients must have received systemic chemotherapy.

- Age greater than or equal to 18 years.

- ECOG performance status less than or equal to 1

- leukocytes >3,000/mcL

- absolute neutrophil count >1,500/mcL

- platelets >90,000/mcL

- total bilirubin <1.5 X institutional upper limit of normal

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

- creatinine within normal institutional limits OR eGFR within normal as predicted
by the CKD-EPI equation > 60 mL/min/1.73 m2.

- The hepatic artery infusion pump chemotherapy has potential teratogenic and/or
abortifacient effects. For this reason, women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry, for the duration of study participation and for 3
months after completion of study treatment. Should a woman become pregnant or suspect
she is pregnant while she or her partner is participating in this study, she should
inform her treating physician immediately.

- Arterial anatomy on CT angiogram amenable to placement of the HAIP.

- Ability of subject to understand and the willingness to sign a written informed
consent document.

- HIV-positive patients may be considered for this study only after consultation with an
HIV trained physician.

EXCLUSION CRITERIA:

- Patients with liver metastases amenable to resection to No Evidence of Disease (NED)
in one stage.

- Patients who are receiving any other investigational agents.

- Patients with incontrovertible radiographic evidence of disease outside of the
colon/rectum (primary) and liver given unlikelihood of benefit from liver-directed
therapy. Patients with indeterminant or low suspicion pulomonary nodules less than 1cm
are included

- Patients who have undergone extra-hepatic metastasectomy and have a documented
disease-free interval less than or equal to 4 months.

- MSI-high patients who need to be treated with a check-point inhibitors

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Active concurrent malignancies within the last five years other than colorectal
primary except basal cell skin carcinoma and thyroid carcinoma.

- Prior radiation to liver.

- Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects of the HAIP chemotherapy. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with HAIP, breastfeeding should be discontinued if the mother is treated. These
potential risks may also apply to other agents used in this study.

- Patients with active Hepatitis B or C infection because of the potential for increased
liver toxicity given the damaging effects of the virus.

- History of allergic reactions attributed to compounds of similar chemical composition
to FUDR or heparin.