Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer
Condition: Liver Metastases; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IV Colon Cancer; Stage IV Rectal Cancer
MeSH terms: Adenocarcinoma; Neoplasm Metastasis; Rectal Neoplasms; Colonic Neoplasms; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Recurrence
Intervention: irinotecan-eluting beads; hepatic artery embolization
Intervention description: Patients will be treated with drug-eluting irinotecan beads per protocol at up to 100 mg per dose every 3 weeks. Patients will receive chemoembolization using LC Bead, loaded with irinotecan. The beads size range used in the study will be 100-300µm (nominal) with a dose of up to 100mg irinotecan per treatment. The beads will be mixed with a non-ionic contrast media in the vial immediately prior to use according to the instructions for use. Irinotecan will be loaded onto the beads not more than 2 hours prior to the procedure. The study goal will be to deliver the full dose of 100mg of irinotecan per treatment; Using a unilateral femoral approach, selective catheterization of the hepatic artery will be performed. Vascular access is obtained via the common femoral artery and a guide-wire advanced under fluoroscopic guidance. A microcatheter is then inserted over the guide-wire. The superior mesenteric artery is selected and an angiogram performed to identify any aberrant arterial anatomy and verify antegrade portal vein flow. The celiac axis is then selected and an angiogram completed. The catheter and guide-wire are used to select the proper hepatic artery and a limited angiogram performed to identify the branches of the hepatic artery. The right or left hepatic artery is selected distal to the cystic artery (if visualized), depending on the location of the lesions to be treated. The LC Bead, loaded with irinotecan will be delivered into the artery.
Intervention MeSH terms: Irinotecan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: The first cohort of patients will receive a dose of 50 mg of irinotecan per DEBIRI treatment. We will escalate by 25 mg with subsequent cohorts up to a dose of 100 mg of irinotecan per DEBIRI treatment.
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      RATIONALE: Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different
      ways to stop the growth of tumor cells, either by killing the cells or stopping them from
      dividing. Chemoembolization kills tumor cells by blocking blood flow to the tumor and keeping
      chemotherapy drugs near the tumor.

      PURPOSE: This phase II trial is studying how well chemoembolization using irinotecan works in
      treating patients with liver metastases from metastatic colon or rectal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a histologically or cytologically confirmed adenocarcinoma of the
             colon or rectum that is metastatic to the liver and for which standard curative
             measures do not exist

          -  Patients must have received prior irinotecan-based treatment for their disease and had
             documented progression by RECIST criteria; patients must also have received prior
             fluoropyrimidine and oxaliplatin-based therapy

          -  Liver disease must not be amenable to potentially curative surgical resection

          -  Patients must have liver-only or liver-predominant disease to be eligible for this
             study; hepatic disease must be dominant, but patients are allowed to have extrahepatic
             disease provided it is not judged likely to be life threatening within 3 months

          -  Patients must have a patent portal vein as documented by CT, MRI, or ultrasound

          -  Prior radiation therapy is allowed but must have been completed >= 4 weeks prior to
             study entry; patients with history of prior radiation to the liver including
             radio-labeled microspheres cannot take part in this study

          -  Eastern Cooperative Oncology Group performance status 0-1

          -  Previous surgery or RFA to the liver is allowed; patients with history of
             chemoembolization or radio-labeled microspheres are excluded

          -  Life expectancy of >= 12 weeks

          -  Leukocytes >= 3,000/uL

          -  Absolute neutrophil count >= 1,500/uL

          -  Platelets >= 100,000/uL

          -  Total bilirubin =< ULN

          -  AST(SGOT)/ALT(SGPT)/Alkaline Phosphatase =< 2.5 X institutional ULN

          -  Creatinine < 2.0 mg/dL

          -  PT/PTT < 1.5 X ULN

          -  Women of childbearing potential (WOCBP) and sexually active males must agree to use an
             accepted and effective method of contraception prior to study entry and for the
             duration of the study; WOCBP include any female who has experienced menarche and who
             has not undergone successful surgical sterilization (hysterectomy, bilateral tubal
             ligation or bilateral oophorectomy) or is not postmenopausal; even women who are using
             oral, implanted or injectable contraceptive hormones or mechanical products such as an
             intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent
             pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy)
             should be considered to be of child bearing potential

          -  Patients must demonstrate ability to understand and the willingness to sign a written
             informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy (including targeted therapy i.e. cetuximab,
             panitumumab) or radiotherapy =< 4 weeks or treatment with bevacizumab =< 6 weeks prior
             to entering the study or those who have not recovered from acute adverse events due to
             agents administered more than 4 weeks earlier, with the exclusion of alopecia or
             neuropathy; patient with history of radiation to the liver including radio-labeled
             microspheres at any point in their past will be excluded

          -  Patients may not be receiving nor have received any other investigational agent =< 4
             weeks prior to study registration

          -  Pregnant or nursing women may not participate in this trial because of the increased
             risk of fetal harm including death from the therapeutic agents

          -  Patients with known brain metastases are excluded from this study because of their
             poor prognosis and frequent development of progressive neurological dysfunction that
             would confound the evaluation of neurologic and other adverse events

          -  As patients with immune deficiency are at increased risk of lethal infections when
             treated with marrow-suppressive therapy, known HIV-positive patients and those with
             known hepatitis B or C are excluded from the study

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             bacterial infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Patients with clinically evident ascites requiring medical management or paracentesis,
             or Childs-Pugh score B/C are not eligible

          -  Patients with evidence of other cancer within 5 years, excluding adequately treated
             basal cell carcinoma of the skin

          -  Patient with significant cardiac, renal or hematologic or pulmonary dysfunction

          -  Patients with previous chemoembolization to liver metastases

          -  Patients may not receive any other anticancer therapy while on study, including
             immunotherapy; patients may not receive any other clinical investigational drug