Microparticle Enhanced Cytotoxic Transarterial Embolization Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine safety and local tumor control of Embozene TANDEM Microspheres (40um TANDEM) loaded with Irinotecan to treat metastatic colorectal carcinoma (mCRC).

Detailed Description
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Colon or rectal carcinoma that has spread to the liver is considered to be metastatic and is a Stage IV cancer. If the metastasized tumor is unresectable, the only current treatment is chemotherapy. Transarterial Chemoembolization (TACE) is considered as a palliative treatment in advanced metastatic colorectal carcinoma (mCRC), with the potential of local tumor control. TACE has evolved in the past 8 years to include drug-delivery devices that can target and deliver drugs from small microparticles (DEB-TACE). Superselective DEB-TACE has the potential to penetrate deeper into the tumor's vasculature to reach peripheral growing points. Loading these microparticles with a cytotoxic drug may improve the level of local tumor control. The MIRACLE III study is a controlled, pilot, single center (Italy) study on 18 subjects with pretreated non-resectable mCRC.

Official Title
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Microparticle Enhanced Cytotoxic Transarterial Embolization Therapy: A Pilot Study of Irinotecan in the Treatment of Metastatic Colorectal Carcinoma (mCRC) by Embozene TANDEM™ Drug-Eluting Microspheres Embolization

Conditions
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Colorectal Carcinoma

Intervention / Treatment
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* Device: 40um Embozene TANDEM Microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female, age >18 yrs who have histologically confirmed adenocarcinoma of the colon or rectum (Stage IV) Presence of metastatic disease with liver as dominant disease-site defined as >80% tumor body burden confined to liver; less than 60% liver tumor replacement. Subject is competent and willing to provide written informed consent in order to participate in the study. Eastern Cooperative Oncology Group (ECOG) performance status is 0-1 or Child-Pugh classification is A or B7. Multinodular or single nodular tumor 4 cm, patients with bilobar disease who can be treated superselectively in a single session or both lobes able to be treated within 3 weeks. Patient must have at least one tumor lesion that meets the following criteria: lesion can be accurately measured in at least one dimension according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Pretreatment with two or more lines of chemotherapy containing Fluorouracil (5-FU) or analogue, oxaliplatin, irinotecan ± bevacizumab ±epidermal growth factor receptor (EGFR)-inhibitors, if indicated, for metastatic disease. No invasion in the blood vessel (hepatic portal, hepatic vein) or bile duct by the computerized axial tomography (CT) or Magnetic Resonance (MR) Imaging. Proper blood, liver, renal, heart function: testing result within 2 weeks from registry of this study as follows: White Blood Cell (WBC) >3,000 cells/mm3 Absolute neutrophil count ≥1500/mm3 International Normalized Ratio (INR) <2.0 Partial Thromboplastin Time (PTT) <40 sec Platelet count >50,000/mm3 Blood bilirubin <3.0 mg/dL Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) is within 5 times of normal range of each organ Serum creatinine <1.5 mg/dL Hemoglobin >8.0 g/dL Alkaline phosphatase <630 IU/L No unstable coronary artery disease or recent Myocardial Infarction(MI) Normal electrocardiogram (ECG) with QT interval <480 msec within the previous 12 months No current infections requiring antibiotic therapy Not on anticoagulation or suffering from a known bleeding disorder. Measureable disease per mRECIST. Expected survival more than 3 months Exclusion Criteria: ECOG performance status >2; or Child-Pugh class>11 points or more, or American Society of Anaesthesiologists' (ASA) class 5 . Bilirubin levels >3 mg/dL mCRC within the large vessel or biliary duct invasion, diffuse hepatocellular carcinoma (HCC) or extrahepatic spread. Patients in which any of the following are contraindicated or present: The use of irinotecan MRI or CT scans Hepatic embolization procedures WBC <3000 cells/mm3 neutrophil <1500 cells/mm3 Cardiac ejection fraction <50% assessed by isotopic ventriculography, echocardiography or MRI Elevated serum creatinine ≥ 2.5 mg/dL Impaired clotting test (platelet count < 50,000/mm3, PT-INR >2.0 AST and/or ALT >5x upper limit of normal (ULN), when greater >250 U/I Known hepatofugal blood flow. Arterio-venous shunt Arterio-portal shunt Main stem portal vein occlusion Women who are pregnant or nursing Allergy to iodinated contrast used for angiography Tumour burden of more than 50% of liver volume (Tumor volume by be smaller e.g. ≤30%) Patients with active bacterial, viral (HIV), or fungal infection. Other malignancies Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient a undue risk what would preclude the safe use of DEB-TACE.

Ages Eligible for Study
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Minimum Age: 19 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 40um Embozene TANDEM Microspheres<br>40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg) | Device: 40um Embozene TANDEM Microspheres<br>* 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom From Serious Adverse Events Rate | Freedom from Serious Adverse Events reports the number of participants that did not have a serious adverse event reported within 30 days of treatment that results in any of the following outcomes: Death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defects. | 30 days | 
| Local Tumor Control | Local tumor control reports the percent of subjects for which the size of the tumor does not increase. Local Tumor Control is defined as subjects having complete response or stable disease. For these subjects the treated tumor either shrinks or stays the same size when measuring the tumor using a standard tumor measurement guideline (based on the devascularization pattern from the European Association for the Study of the Liver (EASL) criteria). | 3 months post procedure | 
| Local Tumor Control | Local tumor control reports the percent of subjects for which the size of the tumor does not increase. Local Tumor Control is defined as subjects having complete response or stable disease. For these subjects the treated tumor either shrinks or stays the same size when measuring the tumor using a standard tumor measurement guideline (based on the devascularization pattern from the European Association for the Study of the Liver (EASL) criteria). | 6 months post procedure | 
| Local Tumor Control | Local tumor control reports the percent of subjects for which the size of the tumor does not increase. Local Tumor Control is defined as subjects having complete response or stable disease. For these subjects the treated tumor either shrinks or stays the same size when measuring the tumor using a standard tumor measurement guideline (based on the devascularization pattern from the European Association for the Study of the Liver (EASL) criteria). | 12 months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival Rate | Number of participants that were alive 12 months after their first study treatment. | 12 months post procedure | 
| Time To Tumor Progression | Time to Tumor Progression is defined as the time from the date of first study treatment to the day of documented disease progression or death due to any cause, whichever came first, assessed up to 1 year. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (mRECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | Up to 12 months post procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Colorectal Carcinoma