LifePearl-Iri Pharmacokinetic Study

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the pharmacokinetic profile, safety, and efficacy of LifePearl microspheres loaded with irinotecan in the treatment of liver predominant mCRC by chemoembolization.

Official Title
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Pharmacokinetic Study In Patients With Liver Predominant Unresectable mCRC Receiving Treatment With LifePearl Microspheres Loaded With Irinotecan

Conditions
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Metastatic Colorectal Cancer, mCRC

Intervention / Treatment
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* Device: TACE with irinotecan loaded LifePearl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is at least 18 years old Histologically proven mCRC At least 1 measurable liver metastasis > 1 cm (mRECIST) Liver predominant disease ( ≥ 80% of metastatic disease confined to the liver) No portal vein involvement Performance status 0 or 1 Life Expectancy ≥ 3m Adequate Hematologic function (ANC≥1.5 10^9/l; PLT≥75 10^9/l; INR (international normalized ratio) ≤1.3) Adequate liver and renal function (Total bilirubin ≤2.0 mg/dl; ALBUMINE 2.5g/dl; Serum creatinine ≤2.0 mg/dl; ALT (alanine transaminase),AST (aspartate transaminase) ≤5 times ULN) Less than 50% liver tumor replacement Patient has provided written informed consent Patient is affiliated to social security or equivalent system (France only) Exclusion Criteria: Eligible for curative treatment (resection/RFA) History of hepaticocholangiojejunostomy or obstructive biliary disease (with/without previous treatment) Previous liver embolization Contraindication for intra-arterial embolization and local irinotecan administration Allergy to contrast media Patient is co-treated with potent CYP3A4/UGT1A1 (cytochrome P450 3A4/uridine diphosphate glucuronosyltransferase 1A1) inducers, i.e. rifampin, rifabutin, phenytoin, phenobarbital, carbamazepine and St John's Wort Patient is currently participating in a clinical trial with an investigational drug or a device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints In the Investigator's opinion patient has (a) co-morbid condition(s) that could limit the patient's ability to participate in the study, compliance with follow-up requirements or impact the scientific integrity of the study Patient is under judicial protection (France only)

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TACE with irinotecan loaded LifePearl<br>10 patients receiving unilobar treatment: day 1=chemoembolization of first lobe of liver, day 14=chemoembolization of second lobe of liver, day 30=chemoembolization of first lobe of liver, day 44= chemoembolization of second lobe of liver; AND 10 patient receiving bilobar treatment: day 1=chemoembolization of both lobes of the liver, day 30=chemoembolization of both lobes of the liver | Device: TACE with irinotecan loaded LifePearl<br>* Arterial embolization will be performed through lobar infusion and using a microcatheter. LifePearl microspheres of 200 µm will be used as preferred beads. They will be loaded with the appropriate dose of irinotecan hydrochloride injectable solution, mixed with the contrast media and distributed to the targeted lobe. The targeted dose is 100 mg of irinotecan per lobe treated, meaning that when treated unilobarly at baseline the total dose received will be 100 mg ( all in one lobe) and in during bilobar treatment, 200 mg in both lobes.<br>* Other names: TACE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Maximum observed plasma concentrations of Irinotecan and its active metabolite SN38 | 2 days | 
| Time to reach Cmax (Tmax) | Tmax will be estimated directly from concentration-time data | 2 days | 
| Area Under the Curve (AUC) | The trapezoidal rule will be used to calculate the area under the curve over 24 hours | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events (AE) (grade ≥3) and Serious AEs related with study treatment up to 30 days post initial treatment |  | 1 month | 
| Overall Survival |  | 12 months | 
| Progression-Free Survival |  | 12 months | 
| Response rate | Response rate (mRECIST criteria) 3 months after the first treatment | 3 months | 
| Technical success - treatment delivery | Ability to deliver ≥75% of the planned dose during the first chemoembolization | 1 day | 
| Technical success - total dose delivered | Sum of all doses delivered during the course of the study | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver, metastatic