LifePearl-Iri Pharmacokinetic Study

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer; mCRC
• Intervention / Treatment: Device: TACE with irinotecan loaded LifePearl

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • KUL
• Germany
  • Heilbronn, Germany
    • SLK-Kliniken Heilbronn GmbH
  • Munich, Germany
    • Klinikum Bogenhausen, Städt. Klinikum München GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TACE with irinotecan loaded LifePearl; 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; 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.; Other Names: TACE

What is the study measuring?

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
Overall Survival		12 months
Adverse Events (AE) (grade ≥3) and Serious AEs related with study treatment up to 30 days post initial treatment		1 month
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

Collaborators and Investigators

• Sponsor: Terumo Europe N.V.
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Federation Francophone de Cancerologie Digestive
• Investigators: Principal Investigator: Hans Prenen, MD, Universitair Ziekenhuis Leuven; Principal Investigator: Philippe Pereira, MD, SLK Kliniken Heilbronn GmbH; Principal Investigator: Julien Taieb, MD, Hôpital Georges Pompidou Paris

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): April 28, 2017
• Study Completion (Actual): September 19, 2017

Study Registration Dates

• First Submitted: August 27, 2015
• First Submitted That Met QC Criteria: September 9, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): November 27, 2017
• Last Update Submitted That Met QC Criteria: November 23, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: metastatic; liver
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: T126E2