RATIONALE: Drugs used in chemotherapy, such as floxuridine and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry cancer-killing substances directly into the liver. Radiolabeled monoclonal antibodies can find tumor cells and carry tumor-killing substances to them without harming normal cells. Giving hepatic arterial infusion of floxuridine together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase I/II trial is studying the side effects and best dose of floxuridine when given as a hepatic arterial infusion together with gemcitabine hydrochloride and radiolabeled monoclonal antibody therapy and to see how well it works in treating liver metastases in patients with metastatic colorectal cancer.
OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and associated toxicities of concurrent hepatic arterial infusion (HAI) fluorodeoxypyrimidine (FUdR)/Decadron and intravenous gemcitabine combined with intravenous yttrium-90 (\^90Y) chimeric T84.66 (cT84.66) in colorectal cancer patients after hepatic resection or maximum surgical debulking (to \< 3 cm) of liver metastases. II. To study the feasibility and toxicities of such adjuvant therapy following resection and/or ablation of liver metastases. III. To evaluate the biodistribution, clearance and metabolism of \^90Y and \^111In (indium-iii) chimeric T84.66 administered intravenously. IV. To estimate radiation doses to whole body, normal organs, and tumor through serial nuclear imaging. V. To correlate proteomic profiles pre and post-therapy with toxicities and anti-tumor effects. OUTLINE: This is a phase I, dose-escalation study of floxuridine followed by a phase II study. Patients receive floxuridine as a continuous hepatic arterial infusion on days 1-14 and gemcitabine hydrochloride IV over 30 minutes on days 9 and 11. Patients also receive yttrium Y 90 anti-CEA monoclonal antibody cT84.66 IV over 25 minutes on day 9. Treatment repeats every 6 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients may receive an additional course of floxuridine in combination with systemic therapy at the discretion of the treating physician. After completion of study treatment, patients are followed up at 3 and 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Given IV
Given via hepatic arterial infusion
Correlative studies
Correlative studies
Correlative studies
Given IV
Correlative studies
Correlative studies
Correlative studies
City of Hope
Duarte, California, United States
Number of Participants With at Least One Dose Limiting Toxicity
Dose Limiting Toxicity (DLT) defined as any treatment-related grade grade 3 nonhematologic toxicity not reversible to grade 2 or less within 24 hours, or any grade 4 toxicity.Up to three cycles of therapy were allowed with DLTs determined based on first cycle tolerance. Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2.0.
Time frame: 4 weeks from start of treatment, up to 2 years.
Recommended Phase II Dose
The maximum tolerated dose (MTD) of HAI FUdR in combination with intravenous gemcitabine and 90Y-DTPA-cT84.66 is based on toxicities observed during the first cycle and is defined as the highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Dose escalations proceeded according to a standard 3+3 design.
Time frame: 4 weeks from start of treatment, up to 2 years.
Overall Survival
Estimated using the product-limit method of Kaplan and Meier. Event defined as death due to any cause.
Time frame: Up to 5 years
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined as a 25% increase in the sum of products of measurable lesions over the smallest sum observed, or appearance of any lesions that had disappeared, or appearance of any new lesion/site.
Time frame: Up to 5 years
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