Clinical trial · Interventional
Expansion of Conventional Criteria for Liver Transplantation in Hepatocellular Carcinoma Through Downstaging
Controlled Expansion of Conventional Criteria for Liver Transplantation in Hepatocellular Carcinoma Through Downstaging Procedures: a Randomized Trial (XXL Trial)
NCT01387503CI-TRIAL-00054383completedN/AClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This clinical trial is aimed at extending the chance of liver transplantation, through downstaging procedures, to patients with hepatocellular carcinoma (HCC) exceeding conventional Milan Criteria. Those patients that will achieve a sustained tumor response after downstaging will be randomized either to undergo liver transplantation or to proceed with conventional non-transplant treatments. The aim of the study is to demonstrate unequivocally that liver transplantation may provide a survival benefit, with an acceptable survival rate of at least 60% at 5 years, to patients that demonstrate a radiological and sustained tumor response after downstaging. Noteworthy is that response is chosen rather than stage migration as endpoint of downstaging.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Carcinoma, Hepatocellular | Hepatocellular Carcinoma | ONTOLOGY_EXACT | 0.98 |
| Cirrhosis | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Liver transplantation | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Group 1 - Transplant strategy
- description
- Patients randomized to Group 1 will be enlisted for liver transplantation and will undergo liver transplantation within 8 months unless oncological (i.e. extrahepatic disease) or medical (i.e. cardiac insufficiency) will occur
- interventionNames
- Procedure: Liver transplantation
- type
- NO_INTERVENTION
- label
- Group 2 - Non-transplant strategy
- description
- Patients randomized to Group 2 will continue to receive treatments according to their stage of disease, or will undergo only strict follow-up should a complete response after downstaging treatments have been achieved
Primary outcomes (2)
- measure
- For Phase II - Time to Tumoral Event (TTE)
- timeFrame
- Every 4 months
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 65 Years
Show eligibility criteria text
Inclusion Criteria: * Patient's age ≥ 18 yrs and ≤ 65 yrs * Presence of cirrhosis of any etiology * Child-Pugh class ≤ B7 * ECOG Performance Status ≤ 1 * Diagnosis of HCC either by biopsy or according to AASLD criteria * HCC exceeding Milan Criteria with a 5-yr estimated survival after transplantation \>50% according to the Metroticket calculator (http://www.hcc-olt-metroticket.org/calculator) * Women of child bearing potential with a negative serum pregnancy test performed before enrolment * Absence of general contraindications to sorafenib/molecular targeted therapies Exclusion Criteria: * Presence of extra-hepatic tumor spread * Presence of macrovascular invasion * Sorafenib therapy started \> 2 months before enrolment * Concurrent cancer, distinct from HCC (except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors) * Previous history of any cancer, even if curatively treated, \< 5 years prior to entry * Active intra-venous or alcohol abusers * HIV infection * History of serious cardiac disease * Severe pulmonary hypertension not treatable by medical therapy * Patients with a life expectancy of less than 3 months due to HCC or less than 6 months due to any other disease
References
Publications (5)
- BACKGROUNDMazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL, Adam R, Neuhaus P, Salizzoni M, Bruix J, Forner A, De Carlis L, Cillo U, Burroughs AK, Troisi R, Rossi M, Gerunda GE, Lerut J, Belghiti J, Boin I, Gugenheim J, Rochling F, Van Hoek B, Majno P; Metroticket Investigator Study Group. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009 Jan;10(1):35-43. doi: 10.1016/S1470-2045(08)70284-5. Epub 2008 Dec 4. PMID 19058754
- BACKGROUNDMazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996 Mar 14;334(11):693-9. doi: 10.1056/NEJM199603143341104. PMID 8594428
- BACKGROUNDLlovet 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
- BACKGROUNDLencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010 Feb;30(1):52-60. doi: 10.1055/s-0030-1247132. Epub 2010 Feb 19. PMID 20175033
- DERIVEDMazzaferro V, Citterio D, Bhoori S, Bongini M, Miceli R, De Carlis L, Colledan M, Salizzoni M, Romagnoli R, Antonelli B, Vivarelli M, Tisone G, Rossi M, Gruttadauria S, Di Sandro S, De Carlis R, Luca MG, De Giorgio M, Mirabella S, Belli L, Fagiuoli S, Martini S, Iavarone M, Svegliati Baroni G, Angelico M, Ginanni Corradini S, Volpes R, Mariani L, Regalia E, Flores M, Droz Dit Busset M, Sposito C. Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial. Lancet Oncol. 2020 Jul;21(7):947-956. doi: 10.1016/S1470-2045(20)30224-2.