Irinotecan -Eluting LC Bead-M1 (DEBIRI-M1) for Patients With Liver Metastases From Colorectal Cancer
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: DEBIRI; LC Bead M1; TACE
Intervention description: Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor.; The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer.; TACE a minimally invasive procedure performed to restrict a tumor's blood supply.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Purpose:

      The purpose of this study is to determine the feasibility and safety of using small beads
      (70-150 micron in place of 100-300 micron) to deliver chemotherapy into the liver to treat
      patients with liver lesions from colorectal cancer. The beads (LC-Bead M1) will be loaded
      with irinotecan (DEBIRI-M1), and used to administer transarterial chemoembolization (TACE).

      Eligibility:

      Patients with liver cancer from colorectal cancer.

      Study Overview/ Treatment:

      DEBIRI, loaded with irinotecan, is a device that utilizes tiny beads (70-150 microns) to
      deliver chemotherapy agents into liver tumor(s) via the hepatic artery. This device allows
      for continuous release of irinotecan into the liver tumor tissue(s) causing necrosis of the
      targeted tumor(s). The potential advantages of the smaller beads are deeper penetration into
      the tumor bed, while avoiding premature proximal occlusion of vessels feeding the tumor, and
      more consistent dosing. Response to therapy will be evaluated monthly by clinic visits and
      blood tests (to include assessment of liver function and tumor markers) and by imaging
      (usually MRIs) every 1-2 months. Patients will be on study for 6 months after which they will
      be exited from the study and followed for survival. Once exited from the study they will
      continue to be eligible to receive DEBIRI, should it be recommended.
    

Eligibility criteria:

        Inclusion Criteria:

        -Patients with a diagnosis of colorectal cancer with hepatic metastases who have failed or
        are intolerant to at least one systemic chemotherapy or liver directed therapy.

          1. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
             at study entry.

          2. The patient is age 18 years or older.

          3. The patient has a life expectancy of >12 weeks.

          4. Patients with liver dominant disease defined as >/=75% tumor body burden confined to
             the liver

          5. Less than 60% liver tumor replacement

          6. At least one month has elapsed since most recent prior cancer therapy with the
             following exception:

             -Chemotherapy (excluding irinotecan based regimens) may continue if there is evidence
             of hepatic progression on treatment providing there is no change in the therapy in the
             1 month prior to DEBIRI-TACE treatment and any immediate chemotherapeutic toxicity
             that will complicate DEBIRI-TACE is resolved. In this case, the chemotherapy may
             continue because it is continuing to control the extrahepatic disease.

          7. The patient has measurable disease that will be directly treated with intrahepatic
             therapy (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).

          8. Patients with at least one measurable liver metastases> 2 cm.

          9. Patients with patent main portal vein

         10. The patient has adequate hematologic function as defined by the following criteria:

             -An absolute neutrophil count (ANC) >/= 1500/mL, Hemoglobin >/= 9.5 g/dL, and a
             Platelet count >/=75,000/mL, INR </=1.3 prior to receiving DEBIRI-TACE.

         11. The patient has adequate hepatic function, as defined by the following criteria:

             -Total bilirubin</= 2.0 mg/dL, Aspartate transaminase (AST) and alanine transaminase
             (ALT) </= 5 x the upper limit of normal (ULN), Albumin >2.

         12. The patient has adequate renal function, as defined by the following criteria:

             -Serum creatinine</=2.0.

         13. The patient has a baseline international normalized ratio (INR)<1.5.

         14. The patient, if a woman of childbearing potential, has a negative pregnancy test.

         15. The patient is able to give written informed consent.

         16. The patient is willing and able to comply with study procedures, scheduled visits, and
             treatment plans.

        Exclusion Criteria:

          1. The patient has a history of another primary cancer (ie, a primary cancer not
             associated with the patient's current liver tumor), with the exception of (a)
             curatively resected nonmelanomatous skin cancer; (b) curatively treated cervical
             carcinoma in situ; or (c) other primary solid tumor treated with curative intent, no
             known active disease present, and no treatment administered during the last 3 years
             prior to enrollment (date of informed consent).

          2. Any contraindication for hepatic embolization procedures:

               -  Large shunt as determined by the investigator (pretesting with TcMMA not
                  required)

               -  Severe atheromatosis

               -  Hepatofugal blood flow

               -  Main portal vein occlusion (e.g. thrombus or tumor)

               -  Any patient eligible for curative treatment (i.e. resection or radiofrequency
                  ablation)

               -  Patients' whose only measurable disease is within an area of the liver previously
                  subject to radiotherapy

          3. Contraindications to irinotecan:

               -  Chronic inflammatory bowel disease and/or bowel obstruction

               -  History of severe hypersensitivity reactions to irinotecan hydrochloride
                  trihydrate, lactic acid or to any of the excipients of Camptosar

               -  Severe bone marrow failure

               -  History of Gilbert Syndrome (specific testing not required)

               -  Concomitant use with St John's Wort (Hypericum)

               -  Marco-shunting noted on the hepatic angiogram.

          4. The patient has untreatable bleeding diathesis.

          5. The patient has complete main portal vein thrombosis with reversal of flow.

          6. The patient has evidence of clinically significant peripheral vascular disease.

          7. The patient has brain metastases

          8. The patient has clinically significant or symptomatic extrahepatic disease, for
             example, an uncontrolled intercurrent illness including, but not limited to:

               -  Ongoing or active infection requiring parenteral antibiotics

               -  Symptomatic congestive heart failure (class II to IV of the New York Heart
                  Association classification for heart disease)

               -  Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within
                  6 months

               -  Uncontrolled hypertension (systolic blood pressure>150 mmHg, diastolic blood
                  pressure>90 mmHg, found on 2 consecutive measurements separated by a 1-week
                  period despite adequate medical support)

               -  Clinically significant cardiac arrhythmia (multifocal premature ventricular
                  contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or
                  requires treatment [NCI-CTCAE Grade 3] or asymptomatic sustained ventricular
                  tachycardia)

          9. The patient is pregnant or breast-feeding.

         10. Psychiatric illness/social situations that would compromise patient safety or limit
             compliance with study requirements

         11. There is evidence of substance abuse or medical, psychological or social conditions
             that may interfere with the patient's participation in the study or evaluation of
             study results

         12. The patient is allergic to contrast media that cannot be readily prevented with
             premedication or managed.

         13. Other significant medical or surgical condition, or any medication or treatment, that
             would place the patient at undue risk and that would preclude the safe use of
             chemoembolization or would interfere with study participation

         14. The patient has peritoneal disease or ascites (greater than trace on imaging).