BioPearl™ Microspheres Loaded With Doxorubicin for the Treatment of Unresectable Hepatocellular Carcinoma (HCC)

Study Overview
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Brief Summary
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The primary objective of the study is to confirm technical success and safety of BioPearl™ microspheres loaded with Doxorubicin in the treatment of unresectable hepatocellular carcinoma (HCC). The secondary objective of the study is to investigate the efficacy of BioPearl™ microspheres loaded with Doxorubicin in the treatment of subjects with unresectable HCC.

Detailed Description
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This is a prospective, single arm, multi-centre, post-market clinical follow-up study to further assess safety and efficacy in 50 subjects with unresectable HCC treated with BioPearl™ microspheres loaded with Doxorubicin. All subjects will undergo clinical follow-up until disease progression and/or next treatment option, after which subjects will be followed for survival. Subjects will be followed up to a maximum of 18 months. An intermediate analysis will take place during enrollment period on safety and technical success to support regulatory requirements.

Official Title
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BioPearl™ Microspheres Loaded With Doxorubicin for the Treatment of Unresectable Hepatocellular Carcinoma (HCC): Prospective, Single Arm, Multi-center, Post-Market Clinical Follow-up (PMCF) Study

Conditions
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Hepatocellular Carcinoma Non-resectable

Intervention / Treatment
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* Device: BioPearl™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 18 years old Subject with HCC confirmed by histology or according to the latest applicable version of (EASL (the European Association for the Study of the Liver) criteria Subject with tumor(s) < 5 cm and within the up to 7 criteria: the sum of the diameter of the largest tumor (in cm) and the number of tumors must be ≤ 7 (see appendix E) BCLC (Barcelona Clinic Liver Cancer) B subject or BCLC A subject not a candidate for curative treatment at the time of study inclusion or who has failed/recurred after resection/ablation. Recurrence in the segment of RFA (Radiofrequency Ablation is not allowed WHO (World Health Organization) or ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1 Subject deemed treatable in one session for initial treatment Normal liver or compensated cirrhosis with preserved liver function (Child-Pugh Class A) Total bilirubin ≤ 2.0 mg/dl Adequate bone marrow function: Hemoglobin ≥ 9g/dl, absolute neutrophil count ≥ 1.0 x 109/L, platelet count ≥ 75 x 109/L Subject with no ascites or with minor ascites controlled by sodium dietary restrictions (subject receiving diuretic treatment or paracentesis is not eligible) Adequate renal function: serum creatinine < 1.5 X ULN (Upper Limit of Normal) Subject has provided written informed consent Subjects of childbearing/reproductive potential should use adequate birth control measures, during the study treatment period until survival follow-up Exclusion Criteria: Subject previously treated with any systemic therapy for HCC Subject previously treated with intra-arterial loco-regional therapy for HCC Prior resection/ablation is allowed as per inclusion criteria 4 Eligible for curative treatment at the time of study inclusion Advanced liver disease: Child-Pugh's B-C class or active gastrointestinal bleeding, encephalopathy Advanced tumoral disease: BCLC class C or D (vascular invasion - even segmental, extra-hepatic spread or cancer-related symptoms performance status >1) History of another primary tumor. Exceptions include: 1) Malignancy treated with curative intent ≥ 5 years before inclusion and with no known active disease / 2) Malignancy which occurred < 5 years before, not active and not expected to recur or be clinically relevant in the next 5 years Subject with history of biliary tree disease or biliary dilatation Portal vein thrombosis, porto-systemic shunt, hepatofugal blood flow or absent portal blood flow in the liver area to be treated Contraindication to multiphasic CT and MRI (e.g. allergy to contrast media) Any other contraindication for embolization procedure or Doxorubicin treatment Subject is currently participating in an investigational drug or device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints Note: Trials requiring extended follow-up for products that were investigational, but have become commercially available since then, are not considered investigational trials In the Investigator's opinion subject has (a) co-morbid condition(s) that could limit the subject's ability to participate in the study, compliance with follow-up requirements or impact the scientific integrity of the study Pregnant or breast-feeding woman

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
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Single arm<br>Transarterial Chemo Embolization (TACE) with BioPearl™ microspheres loaded with Doxorubicin | Device: BioPearl™<br>* TACE<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: by evaluating all procedural or study device related grade 3-4-5 adverse events | Safety: by evaluating all procedural or study device related grade 3-4-5 adverse events (AEs) during a period of 4 weeks post initial treatment as per local investigator assessment | Day 29 | 
| Technical success | Ability to reach near stasis in the treated tumor feeding arteries during chemoembolization procedure | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate | Assessed by mRECIST (modified Response Evaluation Criteria in Solid Tumors) criteria at 4 weeks and every 3 months as per local investigator assessment | 18 months | 
| Progression Free Survival (PFS | Defined as time from the treatment to disease progression according to mRECIST criteria or death from any cause, whichever occurs first as per local investigator assessment | 18 months | 
| Time to progression of treated tumor(s) | Defined as time from treatment to progression of the treated lesion according to mRECIST criteria as per local investigator assessment | 18 months | 
| Duration of response | According to mRECIST as per local investigator assessment | 18 months | 
| Best overall response | Defined as best response of treated tumor(s) recorded during the study according to mRECIST criteria as per local investigator assessment | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma Non-resectable, HCC, TACE, Chemoembolization