Oxaliplatin and Capecitabine With or Without an Hepatic Arterial Infusion With Floxuridine in Treating Patients Who Are Undergoing Surgery and/or Ablation for Liver Metastases Due to Colorectal Cancer
Condition: Colorectal Cancer; Metastatic Cancer
MeSH terms: Colorectal Neoplasms; Neoplasm Metastasis
Intervention: capecitabine; floxuridine; oxaliplatin
Intervention description: Oral capecitabine 850 mg/m2 twice daily on days 1-14 every 21 days for 8 cycles: Arm 1
Oral capecitabine 850 mg/m2 twice daily on days 22-35 every 42 days for 4 cycles and then on days 1-14 every 21 days for 4 cycles: Arm 2; Continuous hepatic arterial infusion of floxuridine 0.2 mg/kg on days 1-14 every 42 days for 4 cycles; Oxaliplatin 130 mg/m2 IV over 2 hours on day 1 every 21 days for 8 cycles: Arm 1
Oxaliplatin 130 mg/m2 IV over 2 hours on day 22 every 42 days for 4 cycles and then on day 1 every 21 days for 4 cycles: Arm 2
Intervention MeSH terms: Capecitabine; Floxuridine; Oxaliplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: liver metastases; stage IV colon cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum

Summary:

      RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, capecitabine, and floxuridine,
      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 tumor-killing
      substances, such as chemotherapy, directly into the liver. Giving chemotherapy in different
      ways may kill more tumor cells. It is not yet known whether giving oxaliplatin and
      capecitabine together with an hepatic arterial infusion with floxuridine is more effective
      than giving oxaliplatin and capecitabine alone in treating patients who are undergoing
      surgery and/or ablation for liver metastases due to colorectal cancer.

      PURPOSE: This randomized phase III trial is studying oxaliplatin, capecitabine, and an
      hepatic arterial infusion with floxuridine to see how well they work compared to oxaliplatin
      and capecitabine in treating patients who are undergoing surgery and/or ablation for liver
      metastases due to colorectal cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically* or cytologically confirmed colorectal adenocarcinoma

               -  No other cellular type (e.g., sarcoma, lymphoma, or carcinoid) NOTE: *If the
                  primary colorectal tumor and the hepatic lesions have been identified at the same
                  time and it is not possible to biopsy the colorectal lesion, the patient will be
                  eligible without histologic confirmation of the colorectal primary cancer as long
                  as other radiographic studies or scans document the characteristics of a
                  colorectal cancer

          -  Synchronous or metachronous metastatic disease confined to the liver

               -  No more than 6 hepatic metastatic lesions that can potentially be resected or
                  ablated

               -  For patients presenting with synchronous lesion(s) in the colon and/or rectum,
                  the primary tumors must, in the opinion of the investigator, appear to be
                  completely resectable

          -  Must be able to undergo surgery and/or ablation within 28 days following randomization

          -  No evidence of extrahepatic metastases

          -  No prior colorectal metastases

          -  No recurrent colorectal cancer concurrent with hepatic metastases

        PATIENT CHARACTERISTICS:

          -  Life expectancy ≥ 5 years, excluding their colorectal cancer

          -  Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1

          -  No other malignancy within the past 5 years except carcinoma in situ of the cervix,
             melanoma in situ, basal cell or squamous cell skin cancer, or carcinoma of the colon
             or rectum

          -  Absolute granulocyte count ≥ 1,200/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  PT/international normalized ratio (INR) ≤ 1.5 unless patient is on therapeutic doses
             of anticoagulant medication

          -  Total bilirubin ≤ upper limit of normal (ULN)

          -  Alkaline phosphatase ≤ 2.5 ULN

          -  aspartate aminotransferase (AST) ≤ 2.5 times ULN

          -  Calculated creatinine clearance > 50 mL/min

          -  Not pregnant or lactating

          -  Negative pregnancy test

          -  Patients with child bearing potential must agree to use adequate contraception

          -  Able to swallow oral medication

          -  No preexisting chronic hepatic disease (e.g., chronic active hepatitis or cirrhosis)

          -  No grade 3 or 4 anorexia or nausea

          -  No vomiting ≥ grade 2

          -  No clinically significant peripheral neuropathy defined as ≥ grade 2 neurosensory or
             neuromotor toxicity

          -  No psychiatric or addictive disorders or other condition that, in the opinion of the
             investigator, would preclude study participation

        PRIOR CONCURRENT THERAPY:

          -  Prior adjuvant fluorouracil alone or in combination with levamisole, leucovorin
             calcium, irinotecan hydrochloride, or oxaliplatin allowed if these regimens were
             completed > 6 months ago

          -  No prior resection/ablation, hepatic arterial infusion therapy, or any systemic
             chemotherapy for metastatic disease

               -  Prior excisional biopsy allowed

          -  No prior radiotherapy to the liver

          -  No concurrent bevacizumab in patients who have had pump/catheter placement receiving
             hepatic arterial infusion of floxuridine

               -  Patients who meet specific situations outlined in the protocol and who have not
                  had pump placement may receive bevacizumab at the physician's discretion

          -  No concurrent halogenated antiviral agents such as sorivudine or brivudine in patients
             receiving fluorouracil, floxuridine, or capecitabine

          -  No concurrent filgrastim (G-CSF), pegfilgrastim, or sargramostim (GM-CSF) as primary
             prophylaxis for neutropenia

               -  Following neutropenic events, these drugs may be used at the physician's
                  discretion during subsequent cycles

          -  No other concurrent cancer therapy

          -  No other concurrent investigational agents