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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00910572
• Other study ID #: INT 30/90
• Status: Completed
• Phase: Phase 2
• First received: May 28, 2009
• Last updated: June 30, 2011
• Start date: July 2007
• Est. completion date: May 2010

Study information

• Verified date: May 2009
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Institute of Health
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Liver Cancer

Intervention

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.

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano	Milano

Sponsors (3)

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

Country where clinical trial is conducted

Italy, 

References & Publications (6)

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression (TTP)		At 1, 3, 6, 12 months and every 6 months thereafter	No
Secondary	Tumor Response according to RECIST, WHO, EASL and Choi criteria		At 3, 6, 12 months and every 6 months thereafter	No
Secondary	Overall survival		At 1, 3, 6, 12 months and every 6 months thereafter	No
Secondary	Safety: documentation of all adverse events		At 1, 3, 6, 12 months and every 6 months thereafter	Yes
Secondary	Time-to-symptomatic progression (TTSP)		At 1, 3, 6, 12 months and every 6 months thereafter	Yes