Chemoembolization Using Irinotecan in Treating Patients With Liver Metastases From Metastatic Colon or Rectal Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: I. To define the response rate of colorectal liver metastases (in the treated lobe) treated with DEBIRI, in refractory mCRC patients. SECONDARY OBJECTIVES: I. To evaluate the time to progression in the treated lobe for this patient population. II. To evaluate the overall survival for this patient population. III. To evaluate patient tolerance and the toxicity profile of treatment with DEBIRI in this patient population. OUTLINE: Patients receive irinotecan-eluting beads via hepatic artery embolization every 3 weeks for up to 3 (unilobar disease) or 4 (bi-lobar disease) courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.

Official Title
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Phase II Study of Drug-eluting Irinotecan Beads (DEBIRI) in Refractory Metastatic Colorectal Cancer With Liver-only or Liver-predominant Disease

Conditions
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Signet Ring Adenocarcinoma of the Colon, Liver Metastases, Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Recurrent Colon Cancer, Recurrent Rectal Cancer, Signet Ring Adenocarcinoma of the Rectum, Stage IV Colon Cancer, Stage IV Rectal Cancer

Intervention / Treatment
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* Combination Product: irinotecan-eluting beads
* Procedure: hepatic artery embolization


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive irinotecan-eluting beads via hepatic artery embolization every 3 weeks for up to 3 (unilobar disease) or 4 (bi-lobar disease) courses in the absence of disease progression or unacceptable toxicity. | Combination Product: irinotecan-eluting beads<br>* 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<br>* Other names: DEBIRI;Procedure: hepatic artery embolization<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression |  | Duration of time from start of treatment to progression | 
| Patient Tolerance and Toxicity Profile |  | First treatment then 30 days after completion of treatment then every 3 months for 2 years | 
| Overall Survival |  | 30 days after completion of treatment then every 3 months for 2 years |