Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy of Liver Metastasis From Colon Cancer With Systemic Fluorouracil, Oxaliplatin, Leucovorin and Bevacizumab

Study Overview
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Brief Summary
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This is a multicentre, open labeled, controlled phase study designed to assess effectiveness of chemoembolization with LC Beads, both with and without systemic chemotherapy, in the treatment of unresectable liver metastases in patients with colorectal cancer.

Detailed Description
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This is a multicentre, open labeled, prospective, randomized, controlled phase I/II study designed to assess the clinical performance of chemoembolization with Low Compression Bead (LC Bead), loaded with irinotecan in combination with intravenous chemotherapy and bevacizumab versus intravenous chemotherapy in combination with bevacizumab in the treatment of unresectable liver metastases in patients with colorectal cancer.

Official Title
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Drug-Eluting Bead, Irinotecan (DEBIRI) Therapy of Liver Metastasis From Colon Cancer With Concomitant Systemic Oxaliplatin, Fluorouracil and Leucovorin Chemotherapy, and Anti-Angiogenic Therapy

Conditions
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Colon Cancer With Metastases to the Liver

Intervention / Treatment
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* Device: LC beads loaded with Irinotecan
* Drug: Oxaliplatin
* Drug: Leucovorin
* Drug: 5-Fluorouracil
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion: Patients over 18 years of age, of any race or sex, who have histologic or radiologic proof of colorectal cancer to the liver, who are able to give informed consent, will be eligible. Patients with at least one measurable liver metastases, with size > 1cm response evaluation criteria in solid tumors (RECIST) Patients with liver dominant disease defined as ≥80% tumor body burden confined to the liver Patients with patent main portal vein Eastern Cooperative Oncology Group (ECOG) Performance Status score of < 2 Life expectancy of > 3 months Non-pregnant with an acceptable contraception in premenopausal women. Hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥75 x109/L, international normalized ratio (INR) ≤1.3* (*If patient is on anticoagulants, they must be able to stop medication temporarily prior to TACE and must have INR ≤1.3 prior to receiving TACE) Adequate liver function as measured by: Total bilirubin ≤ 2.0mg/dl, alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤5 times upper limits of normal (ULN), albumin ≥2.5g/dl, Adequate Hemoglobin and Hematocrit as measured by (Male: for approximate 45 - 62%; and approximate Female: 37 - 48%) or Hemoglobin (Male: approximate 13 - 18 gm/dL Female: approximate 12 - 16 gm/dL). If patient is asymptomatic with Hemoglobin for male 10 to 12.9 or Female 9.5 to 11.9 and do not wish to be transfused they still will be eligible for treatment. Adequate renal function (creatinine ≤ 2.0mg/dl) Women of child bearing potential and fertile men are required to use effective contraception negative serum beta human chorionic gonadotropin (βHCG) Signed, written informed consent Patient is at least one month out from any treatment for Stage III colorectal cancer Patient is at least one year out from any treatment for their Stage IV colorectal cancer. - these patients should not be candidates for curative treatments, and will have recovered from any chemotherapeutic toxicities' they may have experienced. Less than 60% liver tumor replacement Exclusion: Any patient eligible for curative treatment (i.e. resection or radiofrequency ablation). Note: resectability is defined as a single tumor <5cm with adequate liver function defined: Total bilirubin ≤ 2.0mg/dl non-resectability includes patients with greater than 6, tumors close to blood vessels, patients with hepatic-pulmonary shunting, or patients of poor performance Active bacterial, viral or fungal infection within 72 hours of study entry Women who are pregnant or breast feeding Allergy to contrast media that cannot be managed with standard care (e.g. steroids), making magnetic resonance imaging (MRI) or computed tomography (CT) contraindicated. Presence of another malignancy with the exception of cervical carcinoma in situ and stage I basal or squamous carcinoma of the skin. 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) 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 Patients with prior contraindications for the use of irinotecan therapy-this would include 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 or concomitant use with St. John's Wort Patients with prior contraindications for the use of fluorouracil, oxaliplatin, leucovorin or bevacizumab

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LC Beads loaded with Irinotecan and FOLFOX6<br>Device: LC Beads loaded with 100mg Irinotecan Drug: Systemic Chemotherapy (FOLFOX6) Oxaliplatin 85 mg/sqm, IV infusion every two weeks Leucovorin 200mg/sqm, IV infusion every two weeks 5-Fluorouracil 2400mg/sqm, IV infusion every two weeks Bevacizumab 5mg/kg given at the discretion of treating physician | Device: LC beads loaded with Irinotecan<br>* Chemoembolization using LC beads loaded with 100mg Irinotecan<br>* Other names: LC Beads, TACE;Drug: Oxaliplatin<br>* Oxaliplatin 85 mg/sqm, IV infusion every two weeks<br>* Other names: FOLFOX6;Drug: Leucovorin<br>* Leucovorin 200 mg/sqm, IV infusion every two weeks<br>* Other names: FOLFOX6;Drug: 5-Fluorouracil<br>* 5-Fluorouracil 2400 mg/sqm, IV infusion every 2 week<br>* Other names: FOLFOX6;Drug: Bevacizumab<br>* Bevacizumab 5 mg/kg given at the discretion of the treating physician<br>* Other names: Avastin;|
| Active Comparator: FOLFOX6 and Bevacizumab<br>Drug: Systemic Chemotherapy (FOLFOX6) Oxaliplatin 85 mg/sqm, IV infusion every two weeks Leucovorin 200mg/sqm, IV infusion every two weeks 5-Fluorouracil 2400mg/sqm, IV infusion every two weeks Bevacizumab 5mg/kg given at the discretion of treating physician | Drug: Oxaliplatin<br>* Oxaliplatin 85 mg/sqm, IV infusion every two weeks<br>* Other names: FOLFOX6;Drug: Leucovorin<br>* Leucovorin 200 mg/sqm, IV infusion every two weeks<br>* Other names: FOLFOX6;Drug: 5-Fluorouracil<br>* 5-Fluorouracil 2400 mg/sqm, IV infusion every 2 week<br>* Other names: FOLFOX6;Drug: Bevacizumab<br>* Bevacizumab 5 mg/kg given at the discretion of the treating physician<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | Tumor response will be determined using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). Response will classified as: Complete response - disappearance of all lesions; Partial response - at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter or 30% reduction of arterial enhancement; Progressive disease - at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest longest diameter recorded since start of treatment or appearance of one or more new lesions greater than 1cm in size; Stable disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since start of treatment. | Months 2, 4 and 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Serious Adverse Events | Total number of serious adverse events that occurred in both Arms of the study. | First treatment through one year post treatment completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colon cancer, liver metastases