Radioembolization With Yttrium-90 Microspheres for Intermediate or Advanced Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Collaborators:
Gastro Intestinal Surgery and Liver Transplantation
The Hepato-Oncology Group: Department of Surgery, Medicine and Radiology
Information provided by:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier:
NCT00910572
First received: May 28, 2009
Last updated: June 30, 2011
Last verified: May 2009
  Purpose

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).


Condition Intervention Phase
Hepatocellular Carcinoma
Liver Cancer
Device: Yttrium-90 microspheres (Therasphere MDS Nordion)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Radioembolization With Yttrium-90 Microspheres for Intermediate or Advanced HCC (Hepatocellular Carcinoma) Not Eligible to Curative Approach. A Phase II-b Study.

Resource links provided by NLM:


Further study details as provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:

Primary Outcome Measures:
  • Time to progression (TTP) [ Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor Response according to RECIST, WHO, EASL and Choi criteria [ Time Frame: At 3, 6, 12 months and every 6 months thereafter ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter ] [ Designated as safety issue: No ]
  • Safety: documentation of all adverse events [ Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter ] [ Designated as safety issue: Yes ]
  • Time-to-symptomatic progression (TTSP) [ Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: July 2007
Study Completion Date: May 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Device: Yttrium-90 microspheres (Therasphere MDS Nordion)
    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 Name: Therasphere, produced by MDS Nordion, Ottawa, Canada
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of HCC confirmed by histology or non-invasive criteria (EASL/AASLD)
  2. Intermediate stage (BCLC-B) HCC: patients with a large or multinodular HCC (single HCC > 5 cm or multiple HCC defined as > 3 nodules > 3 cm), a Child Pugh class A or B7 and no cancer related symptoms (PS=0-1).
  3. Advanced stage (BCLC-C) HCC: patients with hepatic vascular involvement (at any tumor number and diameter), a Child Pugh class A or B7, no cancer related symptoms (PS=0-1) and absence of extra-hepatic tumor spread.
  4. Cancer-related symptoms within the ECOG 0-1 score
  5. Liver function within Child B-7 class
  6. Platelets > 50.000/µL
  7. WBC > 1500/µL
  8. AST/ALT < 5 times the upper limit of normal (U/L)
  9. Creatinine < 2.0 mg /dL
  10. No indication for any possible curative treatment after multidisciplinary assessment (resection, ablation, transplantation)
  11. Signed informed consent

Exclusion Criteria:

  1. Child-Pugh class higher than B-7 at entry
  2. ECOG performance score ≥ 2 at entry
  3. Tumor volume ≥ 50% of liver volume
  4. Extrahepatic tumor spread
  5. Pulmonary insufficiency
  6. Life expectancy of less than 3 months due to HCC or less than 6 months due to any other disease
  7. Previous chemoembolization procedure (TACE)
  8. Evidence on 99mTc-MAA scan of vascular shunts that can not be corrected by angiographic coil embolization
  9. Evidence on 99mTc-MAA scan of lung shunting, with a potential absorbed dose of radiation to the lungs > 30 Gy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00910572

Locations
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Milano, Italy, 20133
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Gastro Intestinal Surgery and Liver Transplantation
The Hepato-Oncology Group: Department of Surgery, Medicine and Radiology
Investigators
Principal Investigator: Vincenzo Mazzaferro, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr. Vincenzo Mazzaferro, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT00910572     History of Changes
Other Study ID Numbers: INT 30/90
Study First Received: May 28, 2009
Last Updated: June 30, 2011
Health Authority: Italy: National Institute of Health

Keywords provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:
Yttrium-90
Radiation
Radioembolization
Hepatoma
BCLC classification
Hepatic loco-regional treatments
Yttrium
Microspheres

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Liver Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on September 30, 2014