Hepatic Arterial Infusion of Floxuridine, Gemcitabine Hydrochloride, and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer Previously Treated With Surgery
Condition: Liver Metastases; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Neoplasm Metastasis; Rectal Neoplasms; Colonic Neoplasms; Recurrence
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): gemcitabine hydrochloride; floxuridine; proteomic profiling; matrix-assisted laser desorption/ionization time of flight mass spectrometry; liquid chromatography; yttrium Y 90 anti-CEA monoclonal antibody cT84.66; laboratory biomarker analysis; mass spectrometry; pharmacological study
Intervention type(s): Drug; Drug; Genetic; Other; Other; Radiation; Other; Other; Other
Intervention description(s): Given IV; Given via hepatic arterial infusion; Correlative studies; Correlative studies; Correlative studies; Given IV; Correlative studies; Correlative studies; Correlative studies
Other intervention name(s): dFdC; dFdCyd; difluorodeoxycytidine hydrochloride; gemcitabine; Gemzar; LY-188011; 5-FUDR; FdUrD; floxuridin; fluorodeoxyuridine; fluoruridine deoxyribose; FUdR; MALDI-TOF Mass Spectrometry; LC; pharmacological studies
Intervention MeSH terms: Gemcitabine; Floxuridine; Antibodies; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment