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

Primary Purpose

Hepatocellular Carcinoma, Liver Cancer

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Yttrium-90 microspheres (Therasphere MDS Nordion)
Sponsored by
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Yttrium-90, Radiation, Radioembolization, Hepatoma, BCLC classification, Hepatic loco-regional treatments, Yttrium, Microspheres

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Outcomes

Primary Outcome Measures

Time to progression (TTP)

Secondary Outcome Measures

Tumor Response according to RECIST, WHO, EASL and Choi criteria
Overall survival
Safety: documentation of all adverse events
Time-to-symptomatic progression (TTSP)

Full Information

First Posted
May 28, 2009
Last Updated
June 30, 2011
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
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1. Study Identification

Unique Protocol Identification Number
NCT00910572
Brief Title
Radioembolization With Yttrium-90 Microspheres for Intermediate or Advanced Hepatocellular Carcinoma
Official Title
Radioembolization With Yttrium-90 Microspheres for Intermediate or Advanced HCC (Hepatocellular Carcinoma) Not Eligible to Curative Approach. A Phase II-b Study.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2009
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
May 2010 (Actual)

3. Sponsor/Collaborators

Name of the 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

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Liver Cancer
Keywords
Yttrium-90, Radiation, Radioembolization, Hepatoma, BCLC classification, Hepatic loco-regional treatments, Yttrium, Microspheres

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Device
Intervention Name(s)
Yttrium-90 microspheres (Therasphere MDS Nordion)
Other Intervention Name(s)
Therasphere, produced by MDS Nordion, Ottawa, Canada
Intervention Description
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.
Primary Outcome Measure Information:
Title
Time to progression (TTP)
Time Frame
At 1, 3, 6, 12 months and every 6 months thereafter
Secondary Outcome Measure Information:
Title
Tumor Response according to RECIST, WHO, EASL and Choi criteria
Time Frame
At 3, 6, 12 months and every 6 months thereafter
Title
Overall survival
Time Frame
At 1, 3, 6, 12 months and every 6 months thereafter
Title
Safety: documentation of all adverse events
Time Frame
At 1, 3, 6, 12 months and every 6 months thereafter
Title
Time-to-symptomatic progression (TTSP)
Time Frame
At 1, 3, 6, 12 months and every 6 months thereafter

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of HCC confirmed by histology or non-invasive criteria (EASL/AASLD) 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). 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. Cancer-related symptoms within the ECOG 0-1 score Liver function within Child B-7 class Platelets > 50.000/µL WBC > 1500/µL AST/ALT < 5 times the upper limit of normal (U/L) Creatinine < 2.0 mg /dL No indication for any possible curative treatment after multidisciplinary assessment (resection, ablation, transplantation) Signed informed consent Exclusion Criteria: Child-Pugh class higher than B-7 at entry ECOG performance score ≥ 2 at entry Tumor volume ≥ 50% of liver volume Extrahepatic tumor spread Pulmonary insufficiency Life expectancy of less than 3 months due to HCC or less than 6 months due to any other disease Previous chemoembolization procedure (TACE) Evidence on 99mTc-MAA scan of vascular shunts that can not be corrected by angiographic coil embolization Evidence on 99mTc-MAA scan of lung shunting, with a potential absorbed dose of radiation to the lungs > 30 Gy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincenzo Mazzaferro, MD
Organizational Affiliation
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
City
Milano
ZIP/Postal Code
20133
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
16371529
Citation
Salem R, Lewandowski RJ, Atassi B, Gordon SC, Gates VL, Barakat O, Sergie Z, Wong CY, Thurston KG. Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival. J Vasc Interv Radiol. 2005 Dec;16(12):1627-39. doi: 10.1097/01.RVI.0000184594.01661.81.
Results Reference
background
PubMed Identifier
18989675
Citation
Vente MA, Wondergem M, van der Tweel I, van den Bosch MA, Zonnenberg BA, Lam MG, van Het Schip AD, Nijsen JF. Yttrium-90 microsphere radioembolization for the treatment of liver malignancies: a structured meta-analysis. Eur Radiol. 2009 Apr;19(4):951-9. doi: 10.1007/s00330-008-1211-7. Epub 2008 Nov 7.
Results Reference
background
PubMed Identifier
18391616
Citation
Dawson LA, Guha C. Hepatocellular carcinoma: radiation therapy. Cancer J. 2008 Mar-Apr;14(2):111-6. doi: 10.1097/PPO.0b013e31816a0e80.
Results Reference
background
PubMed Identifier
16250051
Citation
Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma. Hepatology. 2005 Nov;42(5):1208-36. doi: 10.1002/hep.20933. No abstract available.
Results Reference
background
PubMed Identifier
18477802
Citation
Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008 May 21;100(10):698-711. doi: 10.1093/jnci/djn134. Epub 2008 May 13.
Results Reference
background
PubMed Identifier
18027884
Citation
Kulik LM, Carr BI, Mulcahy MF, Lewandowski RJ, Atassi B, Ryu RK, Sato KT, Benson A 3rd, Nemcek AA Jr, Gates VL, Abecassis M, Omary RA, Salem R. Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis. Hepatology. 2008 Jan;47(1):71-81. doi: 10.1002/hep.21980.
Results Reference
background
PubMed Identifier
22911442
Citation
Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, Maccauro M, Marchiano A, Bongini M, Lanocita R, Civelli E, Bombardieri E, Camerini T, Spreafico C. Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology. 2013 May;57(5):1826-37. doi: 10.1002/hep.26014. Epub 2013 Mar 22.
Results Reference
derived

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

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