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

June 30, 2011 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Radioembolization With Yttrium-90 Microspheres for Intermediate or Advanced HCC (Hepatocellular Carcinoma) Not Eligible to Curative Approach. A Phase II-b Study.

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milano, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to progression (TTP)
Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter
At 1, 3, 6, 12 months and every 6 months thereafter

Secondary Outcome Measures

Outcome Measure
Time Frame
Tumor Response according to RECIST, WHO, EASL and Choi criteria
Time Frame: At 3, 6, 12 months and every 6 months thereafter
At 3, 6, 12 months and every 6 months thereafter
Overall survival
Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter
At 1, 3, 6, 12 months and every 6 months thereafter
Safety: documentation of all adverse events
Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter
At 1, 3, 6, 12 months and every 6 months thereafter
Time-to-symptomatic progression (TTSP)
Time Frame: At 1, 3, 6, 12 months and every 6 months thereafter
At 1, 3, 6, 12 months and every 6 months thereafter

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

November 1, 2009

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

May 28, 2009

First Submitted That Met QC Criteria

May 29, 2009

First Posted (Estimate)

June 1, 2009

Study Record Updates

Last Update Posted (Estimate)

July 1, 2011

Last Update Submitted That Met QC Criteria

June 30, 2011

Last Verified

May 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INT 30/90

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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