Clinical trial NCT00867750: SIR-Spheres® Microspheres Versus Transarterial Chemoembolisation in Patients With Unresectable Hepatocellular Carcinoma
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: HCC
RE
Yttrium-90
SIR-Spheres microspheres
TACE
Radioembolisation
Transarterial Chemoembolisation
Lead sponsor: Sirtex Medical
Sponsor class: INDUSTRY
First posted: 2009-03-24
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Health-related quality of life (HRQL)
timeFrame: 9 months
Secondary outcomes:
measure: Progression Free Survival (PFS); calculated from the date of first treatment
timeFrame: From the date of first treatment until disease progression
measure: Morphological tumour response; assessed using RESIST criteria
timeFrame: From the date of first treatment until disease progression
measure: Functional tumour response; assessed via tumour marker reduction
timeFrame: From the date of first treatment until disease progression
measure: Survival at 6 and 12 months
timeFrame: 6 and 12 months from the date of first treatment
measure: Overall survival
timeFrame: From the date of first treatment until death
measure: Incidence rate of portal vein invasion
timeFrame: From the date of first treatment until disease progression
measure: Incidence rate of extra-hepatic disease
timeFrame: From the date of first treatment until disease progression
measure: Pharmaco-economic assessment
timeFrame: 9 months
Other outcomes:
Locations:
city: München
country: Germany
facility: Universitäts-Klinikum München-Grosshadern, Medizinische Klinik und Poliklinik II
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
Study officials:
affiliation: Clinica Universitaria de Navarra
name: Dr Bruno Sangro, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitäts-Klinikum München-Grosshadern
name: Dr. Frank Kolligs, PD
role: PRINCIPAL_INVESTIGATOR
References: