HepaSphere™ Microspheres Prospective Registry

Study Overview
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Brief Summary
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HepaSphere™ Microspheres loaded with irinotecan received CE mark for the indication of use in embolization of metastatic colorectal cancer (mCRC) to the liver in 2015. The purpose of this registry is to demonstrate the safety and efficacy of HepaSphere Microspheres loaded with irinotecan for the treatment of colorectal liver metastasis and add to the understanding of the use and value of this treatment in 'real life' usage conditions.

Detailed Description
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This prospective, post-market study was designed to evaluate the median overall survival (MOS) of subjects with metastatic colorectal cancer (mCRC) to the liver treated with HepaSphere Microspheres loaded with the chemotherapeutic agent irinotecan. This treatment process is referred to as transarterial chemoembolization (TACE). Subjects with confirmed colorectal cancer liver metastases that were ineligible for surgical hepatic tumor resection and that had not undergone prior TACE for this indication were considered for study participation. Patients that met eligibility criteria, wanted to participate in the study, and signed the informed consent form (ICF) made up the study subject population. All study subjects were in one cohort and were not blinded to treatment. Per protocol, all subjects completed a baseline visit to collect medical history information, lab assessments, and have a baseline MRI. Following this baseline visit subjects were to have two TACE cycles (i.e., TACE Cycle 1, TACE Cycle 2), with TACE Cycle 2 occurring within 2-4 weeks following TACE Cycle 1. A TACE cycle is defined as one TACE procedure for subjects with unilobar disease or two TACE procedures for subjects with bilobar disease (i.e., one for each lobe of the liver). Following completion of TACE Cycle 1 and TACE Cycle 2, additional TACE cycles could be performed at the investigator's discretion for residual or new disease. When subjects had completed two TACE cycles and were no longer indicated for further TACE cycles (at the investigator's discretion), they entered follow-up. The study ended and analysis began when all enrolled subjects had (1) completed two-year (24 months) follow-up from the date of TACE Cycle 1, (2) been deemed lost to follow up, or (3) died, whichever occurred first.

Official Title
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Prospective Registry of Transarterial Chemoembolization of Metastatic Colorectal Cancer to the Liver With HepaSphere™ Microspheres Loaded With Irinotecan

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Device: HepaSphere Microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or radiologically confirmed colorectal cancer metastases to the liver Patient is able to have either CT or MRI imaging Hepatic tumor burden ≥50% of total tumor burden Hepatic tumor burden ≤50% of total liver volume Not suitable for treatment by resection or percutaneous ablation at time of TACE treatment Life expectancy ≥ 3 months WHO performance status ≤ 2 Exclusion Criteria: Previous treatment with any form of hepatic transarterial embolization Total bilirubin ≥ 3.0 mg/dL Any contraindication for irinotecan administration Partial or complete thrombosis of the main portal vein Cardiovascular or respiratory failure Any other condition deemed exclusionary by the Investigator
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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: HepaSphere Microspheres|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Median overall survival of subjects treated with HepaSphere Microspheres loaded with irinotecan. Analysis will be performed when all subjects enrolled have been followed for survival for two years (24 months), are considered lost to follow up, or have died, whichever comes first | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Determined by the Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) when all subjects enrolled have been followed for survival for 2 years (from date of 1st TACE), are considered lost to follow up, or have died, whichever comes first. Per mRECIST (target lesions assessed by MRI): Complete Response (CR), at least >=30% decrease in the sum of diameters of all viable target lesions, Partial Response (PR), at least a >=30% decrease in the sum of diameters of all viable target lesions, Stable Disease (SD), any cases that do not qualify for either partial response or progressive disease, Progressive Disease (PD), An increase of at least 20% in the sum of the diameters of or viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since started. Overall Response (OR) = CR + PR. ORR is calculated as= (no. of patients with CR + the no. of patients with PR) / N. (N= No of participants analyzed) | 24 months | 
| Best Tumor Response | Per the Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) for target lesions and assessed by MRI: Complete Response (CR), at least > =30% decrease in the sum of diameters of all viable ( enhancement in the arterial phase) target lesions, Partial Response (PR), at least a >=30% decrease in the sum of diameters of all viable (enhancement in the arterial phase) target lesions, Stable Disease (SD), any cases that do not qualify for either partial response or progressive disease, Progressive Disease (PD), An increase of at least 20% in the sum of the diameters of or viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since started. Best Tumor Response (BTR) was assessed during the period of time between TACE Cycle 1 and the last post-TACE MRI or CT. BTR will be presented as the number of subjects within each response category and percentage of evaluated subjects. | 24 months | 
| Liver Progression-free Survival | Median liver progression-free survival will be calculated as the time (in months) between the first TACE procedure to the date on which progression of the subject's liver metastases was documented or the date of death (from any cause). Per the Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) for target lesions and assessed by MRI, Progressive Disease (PD) is defined as an increase of at least 20% in the sum of the diameters of or viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since started. | 24 months | 
| Time to Progression | Time to Progression (TTP) was defined as the length of time between TACE Cycle 1 and disease progression (as determined by MRI or CT imaging) of both hepatic and extrahepatic disease. The date of the first study TACE was time zero. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal Cancer, Liver metastases, Transarterial chemoembolization