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

NCT00910572 | Completed Phase 2

• 1 other identifier: INT 30/90
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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).

Conditions

Hepatocellular Carcinoma; Liver Cancer

Keywords

Yttrium-90; Radiation; Radioembolization; Hepatoma; BCLC classification; Hepatic loco-regional treatments; Yttrium; Microspheres

Outcome Measures

Primary Outcomes (1)

• Time to progression (TTP)

  At 1, 3, 6, 12 months and every 6 months thereafter

Secondary Outcomes (4)

• Tumor Response according to RECIST, WHO, EASL and Choi criteria

  At 3, 6, 12 months and every 6 months thereafter

• Overall survival

  At 1, 3, 6, 12 months and every 6 months thereafter

• Safety: documentation of all adverse events

  At 1, 3, 6, 12 months and every 6 months thereafter

• Time-to-symptomatic progression (TTSP)

  At 1, 3, 6, 12 months and every 6 months thereafter

Interventions

Yttrium-90 microspheres (Therasphere MDS Nordion) DEVICE

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.

Also known as: Therasphere, produced by MDS Nordion, Ottawa, Canada

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Gastro Intestinal Surgery and Liver Transplantation: collaborator
• The Hepato-Oncology Group: Department of Surgery, Medicine and Radiology: collaborator

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Milan, 20133, Italy

Location

Related Publications (7)

• 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.

  PMID: 16371529 BACKGROUND

• 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.

  PMID: 18989675 BACKGROUND

• Dawson LA, Guha C. Hepatocellular carcinoma: radiation therapy. Cancer J. 2008 Mar-Apr;14(2):111-6. doi: 10.1097/PPO.0b013e31816a0e80.

  PMID: 18391616 BACKGROUND

• 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.

  PMID: 16250051 BACKGROUND

• 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.

  PMID: 18477802 BACKGROUND

• 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.

  PMID: 18027884 BACKGROUND

• 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.

  PMID: 22911442 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Vincenzo Mazzaferro, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 28, 2009
• First Posted: June 1, 2009
• Study Start: July 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: May 1, 2010
• Last Updated: July 1, 2011

Record last verified: 2009-05

Locations

IT (1)