Radioembolization With Yttrium-90 Microspheres for Intermediate or Advanced Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma; Liver Cancer
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional
Phase: Phase 2

Summary: 
      Rationale: Patients diagnosed with hepatocellular carcinoma (HCC) at an intermediate or
      advanced stage (according to the BCLC classification system) are not amenable of curative
      treatment. According to EASL and AASLD guidelines patients with an intermediate stage HCC are
      treated with trans-arterial chemoembolization (TACE) while patients with an advanced stage
      HCC are treated with molecular targeted drugs or other combinations according to their liver
      function. The median survival expected for patients in intermediate-advanced stages ranges
      from 11 to 20 months.

      Purpose of the Study: The purpose of this prospective phase II study is to determine whether
      or not Radioembolization with Yttrium-90 microspheres (TheraSphere®) provides an anti-tumoral
      effect and a sensible benefit in terms of time-to-progression (TTP) and survival in patients
      with good liver function (Child A-B7) and a confirmed diagnosis of Intermediate or Advanced
      (because of the presence of neoplastic portal thrombosis) Hepatocellular Carcinoma (HCC).
    

Detailed description: 
      Patients at an intermediate stage (BCLC-B) are currently offered trans-arterial
      chemoembolisation (TACE) as the standard of care. A recent meta-analysis showed that
      radioembolization with beta-emitting Yttrium-90-loaded glass microspheres (TheraSphere®) in
      patients with HCC achieves a median objective response in 79% of cases (range 29-88%) and
      median survival exceeding 15 months has been reported in patients at intermediate stages who
      have been treated with TheraSphere®.

      In patients with HCC at an advanced stage (BCLC-C) the single treatment that has shown a
      statistical advantage on overall survival and disease progression is sorafenib, that provides
      a median survival of 10.7 months. Based on the results reported in literature, the estimated
      median expected survival of patients with advanced HCC treated by TheraSphere® can be as long
      as 12 months.

      After approval on July 2007 of a treatment protocol of Y-90 for compassionate use by the
      institutional IRB, at the National Cancer Institute of Milan 40 consecutive patients have
      been treated with radioembolization with Yttrium-90 microspheres (Theraspheres®) according to
      the same guidelines of the present prospective phase II protocol. The initial series of 40
      patients treated according to a compassionate use of Y-90 has been instrumental for the
      assessment of the procedure's safety and tolerability. The present study has been targeted to
      60 cases including the fist series of 40 "compassionate" patients, due to their adherence to
      the same inclusion/exclusion criteria of the proposed phase II study.
    

Intervention name(s): Yttrium-90 microspheres (Therasphere MDS Nordion)
Intervention type(s): Device
Intervention description(s): Y-90 is incorporated into very tiny glass beads (microspheres: Therasphere MDS Nordion) and is injected into the liver tumor through the hepatic arteries, which are responsible for the feeding of the neoplastic liver tissue. Since the microspheres are unable to pass through the micro-vasculature of the liver parenchyma and tumor they are trapped at those sites and exert a local radio-therapeutic effect.
Other intervention name(s): Therasphere, produced by MDS Nordion, Ottawa, Canada
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Yttrium-90; Radiation; Radioembolization; Hepatoma; BCLC classification; Hepatic loco-regional treatments; Yttrium; Microspheres