SIR-Spheres® Microspheres Versus Transarterial Chemoembolisation in Patients With Unresectable Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
This study is open to patients with primary HCC who cannot be treated by potentially curative treatment modalities, such as surgical resection, liver transplantation or percutaneous ablation. Patients that satisfy the study eligibility criteria will be randomised in a 1: 1 ratio to receive either Radioembolisation with SIR-Spheres Microspheres or the standardised Transarterial Chemoembolisation procedure. Study Objectives This study will evaluate and compare quality of life as well as safety and efficacy of RE or TACE in patients with unresectable HCC. Patients will be followed for a minimum of 12 months or until death wherever possible in the evaluation of the primary and secondary objectives of this study.

Official Title
-----------------
Radioembolisation (RE) With SIR-Spheres® Microspheres Versus Transarterial Chemoembolisation (TACE) in Patients With Unresectable Hepatocellular Carcinoma (HCC). A Comparative, Prospective, Randomised, Open, Pilot Study.

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Device: Radioembolisation (SIR-Spheres® microspheres)
* Drug: Transarterial Chemoembolisation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patients, aged ≥ 18 years Unequivocal diagnosis of primary HCC (confirmed by biopsy/histology or EASL criteria) Tumour characteristics as follows: Not more than 5 lesions If single, maximal diameter ≤ 10 cm If multiple, sum of maximal diameters ≤ 15 cm Lesions satellite to primary tumour of less than 1 cm in maximal diameter are not included At least one quantifiable lesion on hepatic MRI Preserved liver function, corresponding to Child-Pugh class ≤ B-7 ECOG performance status ≤ 2 Life expectancy ≥ 12 weeks Female patients of childbearing potential must have a negative pregnancy test prior to inclusion in the trial and male and female patients must agree to use an effective contraceptive method for the duration of the trial. Willing and able to provide written informed consent Exclusion Criteria: Patients expected to undergo surgery (resection or transplantation) within the 24-week period after randomisation. Ascites, which is detectable on physical examination or clinically symptomatic (but patients having ascites discovered by imaging only should not be excluded). Serum transaminases > 5 x ULN Lung shunt > 20% Extrahepatic disease Moderate to severe portal hypertension, as evidenced by any of the following criteria (occurring in spite of using common criteria for prophylactic treatment and therapy): History of variceal haemorrhage in past 2 years History of hepatic encephalopathy Platelets < 50.000 /ml WBC < 3.000 / ml Previous TIPSS procedure Portal vein occlusion or hepatofugal flow. Impaired liver function Total serum bilirubin > 2.0 mg / dL Serum albumin < 3.0 g /dl creatinine > 2 mg / dL Chemotherapy or other experimental therapy within preceding 4 weeks Previous TAE / TACE Previous radiation therapy to liver or lungs Contraindications for angiography (severe peripheral vascular disease or uncorrectable bleeding diathesis) Anatomical variants apparent on 99mTc-MAA scan precluding safe administration of RE Any decompensated concomitant disease Female patients who are pregnant, breast-feeding, or pre-menopausal and not practising efficient contraceptive method (hormonal contraceptive, intra-uterine device)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RE<br>Device: Radioembolisation with yttrium-90 labelled SIR-Spheres microspheres | Device: Radioembolisation (SIR-Spheres® microspheres)<br>* Yttrium-90 SIR-Spheres microspheres<br>|
| Active Comparator: TACE<br>Transarterial Chemoembolisation with embolising agent Embospheres and chemotherapeutic agent epirubicin | Drug: Transarterial Chemoembolisation<br>* TACE with embolising agent Embospheres (150-300 μm or 300-500 μm diameter) with 50 mg of chemotherapeutic agent epirubicin admixed with 5 ml lipiodol.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-related quality of life (HRQL) |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS); calculated from the date of first treatment |  | From the date of first treatment until disease progression | 
| Morphological tumour response; assessed using RESIST criteria |  | From the date of first treatment until disease progression | 
| Functional tumour response; assessed via tumour marker reduction |  | From the date of first treatment until disease progression | 
| Survival at 6 and 12 months |  | 6 and 12 months from the date of first treatment | 
| Overall survival |  | From the date of first treatment until death | 
| Incidence rate of portal vein invasion |  | From the date of first treatment until disease progression | 
| Incidence rate of extra-hepatic disease |  | From the date of first treatment until disease progression | 
| Pharmaco-economic assessment |  | 9 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCC, RE, Yttrium-90, SIR-Spheres microspheres, TACE, Radioembolisation, Transarterial Chemoembolisation