Combination Chemotherapy and Bevacizumab Before Surgery and Radiolabeled Monoclonal Antibody Therapy in Treating Liver Metastases in Patients With Metastatic Colorectal Cancer
Condition: Liver Metastases; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer
MeSH terms: Neoplasm Metastasis; Rectal Neoplasms; Colonic Neoplasms; Recurrence
Intervention: oxaliplatin; leucovorin calcium; fluorouracil; bevacizumab; yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A; laboratory biomarker analysis; pharmacological study; irinotecan hydrochloride
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Correlative studies; Correlative studies; Given IV
Intervention MeSH terms: Leucovorin; Bevacizumab; Antineoplastic Agents, Immunological; Fluorouracil; Oxaliplatin; Irinotecan; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving combination chemotherapy and bevacizumab before
      surgery and radiolabeled monoclonal antibody therapy works in treating liver metastases in
      patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as leucovorin
      calcium, fluorouracil, and oxaliplatin (FOLFOX), work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal
      antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the
      ability of tumor to grow and spread. Others find tumor cells and help kill them or carry
      tumor-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90
      DOTA anti-CEA monoclonal antibody M5A, can find tumor cells and carry tumor-killing
      substances to them without harming normal cells. Giving chemotherapy and monoclonal antibody
      before surgery may make the tumor smaller and reduce the amount of normal tissue that needs
      to be removed. Giving radiolabeled monoclonal antibody therapy after surgery may kill any
      tumor cells that remain after surgery
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a Karnofsky performance status of >= 60%

          -  Patients must have histological confirmation of colorectal carcinoma

          -  Patients must have colorectal tumors that produce carcinoembryonic antigen (CEA) as
             documented by either immunohistochemistry or by an elevated serum CEA

          -  Patients will be enrolled on this trial after resection of hepatic metastases combined
             with FOLFIRI or FOLFOX [+/- Bevacizumab], or XELOX; patients may have received a
             maximum of 12 cycles of FOLFIRI or FOLFOX [+/- Bevacizumab], or XELOX, which includes
             chemotherapy prior to and post hepatic resection

          -  Prior radiotherapy, immunotherapy, or chemotherapy must have been completed between
             4-12 weeks prior to patient entry on this study and patients must have recovered from
             all expected acute side effects of the prior therapy

          -  Hemoglobin >= 10 gm %; patients may be transfused to reach a hemoglobin >= 10 gm %

          -  White blood cell (WBC) >= 4000/uL

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelets >= 150,000/ul

          -  Patients may have history of prior malignancy for which the patient has been
             disease-free for five years; basal or squamous cell skin cancers or carcinoma in situ
             of the cervix are allowed regardless of diagnosis date

          -  Patients must have no prior history of radiation therapy to the liver (includes 90Y
             microsphere therapy)

          -  Patients must have a total bilirubin =< 1.5 mg/dL

          -  Serum creatinine of =< 1.5 x upper limit of normal (ULN)

          -  Patients must have had < 40% liver resected at the close of completion of the hepatic
             resection; this will be verified retrospectively

          -  Serum human immunodeficiency virus (HIV) testing and hepatitis B surface antigen and
             hepatitis C antibody testing must be negative

          -  Women of childbearing potential must have a negative serum pregnancy test prior to
             entry and while on study must be practicing an effective form of contraception

          -  If a patient has previously received murine or chimeric antibody, then serum
             anti-antibody testing must be negative

          -  Computed tomography (CT) scan restaging done prior to RIT must demonstrate no evidence
             of progressive disease

          -  The patient must be seen in consultation by the radiation oncologist who will be
             administering the radiolabeled antibody therapy and must be informed of the potential
             risks and side effects of the therapy, and informed consent must be documented in the
             consultation note

        Exclusion Criteria:

          -  Patients that have received radiation therapy to greater than 50% of their bone marrow

          -  Patients with any nonmalignant intercurrent illness (example cardiovascular,
             pulmonary, or central nervous system disease) which is either poorly controlled with
             currently available treatment or which is of such severity that the investigators deem
             it unwise to enter the patient on protocol shall be ineligible

          -  Chronic active hepatitis, cirrhosis, or chemotherapy steatohepatitis