Expansion of Conventional Criteria for Liver Transplantation in Hepatocellular Carcinoma Through Downstaging
|ClinicalTrials.gov Identifier: NCT01387503|
Recruitment Status : Unknown
Verified June 2011 by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
Recruitment status was: Recruiting
First Posted : July 4, 2011
Last Update Posted : July 4, 2011
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.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Hepatocellular Cirrhosis||Procedure: Liver transplantation||Phase 2 Phase 3|
Patients that will be considered eligible for the study will undergo downstaging procedures according their stage of disease and to Center's policies. Length and intensity of downstaging will be center specific and not centrally pre-determined, but should be inferior to 18 months. Downstaging procedures will be stopped when, according to the Investigators' judgement, the best possible tumor response has been achieved: at this timepoint a radiological evaluation of tumor response according to modified RECIST (mRECIST) criteria will be performed. Patients that have achieved a Complete or Partial Response (PR or CR) will proceed to Bridging Phase, while those with a Stable or Progressive disease (SD or PD) will drop-out from the study.
Patients that achieved PR or CR after downstaging will receive systemic therapy with sorafenib for three months. After three months radiological response will be assessed according to mRECIST criteria. If a sustained response will be demonstrated patients will proceed to randomization. PD during bridging phase will cause drop-out from the study.
- Randomization and study period
Patients will be randomized in a 1:1 ratio, using computer generated list stratified by Center and by compliance to sorafenib treatment (based on whether ≤50% or > 50% of the standard dosage (800 mg/day) has been administered).
- The experimental group (Group 1 - transplant strategy) will be enlisted for transplantation and will undergo liver transplantation within 8 months unless major medical or oncological contraindications should occur.
- The control group (Group 2 - non-transplant strategy) will continue with sorafenib until progression. Then they may be treated with either medical or locoregional/surgical therapies according to best practice and Centers' policy, excluding transplantation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||260 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Controlled Expansion of Conventional Criteria for Liver Transplantation in Hepatocellular Carcinoma Through Downstaging Procedures: a Randomized Trial (XXL Trial)|
|Study Start Date :||January 2011|
|Estimated Primary Completion Date :||January 2013|
|Estimated Study Completion Date :||January 2014|
Experimental: Group 1 - Transplant strategy
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
Procedure: Liver transplantation
Once randomized to Group 1, patients will be enlisted for liver transplantation at the recruiting Center. Prioritization is encouraged as a waiting time of more than 8 months could cause patients' drop-out from the study
No Intervention: Group 2 - Non-transplant strategy
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
- For Phase II - Time to Tumoral Event (TTE) [ Time Frame: Every 4 months ]TTE after randomization will be calculated as the interval between the randomization date and the date of tumour recurrence for tumor-free patients (either because of liver transplantation or complete response after downstaging procedures) or the date of tumour progression otherwise, with censoring at the date of last contact for event-free patients.
- For Phase III - Overall Survival [ Time Frame: Every 4 months ]Time form the date of randomization and the date of death, with censoring at the date of last contact for event-free patients
- Transplant vs. non transplant strategy cost-benefit analysis [ Time Frame: Approx. 1 year after the last patient randomized ]Comparison between the cost/benefit of a downstaging strategy followed by liver transplantation (treatment group) Vs the cost/benefit of convenional therapies (control group), analyzed according to the Quality Adjusted Life Years (QALY) gained in the treatment group
- Validation of modified RECIST criteria of radiological response to downstaging treatments [ Time Frame: Approx. 8 months after the last patient randomized ]Radiology/pathology correlation on efficacy of downstaging treatments in achieving tumor response, as a basis for possible validation of modified RECIST criteria.
- Validation of the Metroticket model for the prognosis of survival after liver transplantation in patients exceeding Milan Criteria [ Time Frame: Approx. 1 year after the last patient randomized ]http://www.hcc-olt-metroticket.org/calculator/
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01387503
|Contact: Vincenzo Mazzaferro, MD||+39 02 23902760||Trial.XXL@istitutotumori.mi.it|
|Ospedali Riuniti di Bergamo||Recruiting|
|Bergamo, Italy, 24125|
|Ospedale Maggiore di Milano Policlinico||Recruiting|
|Milano, Italy, 20122|
|Istituto Nazionale Tumori||Recruiting|
|Milano, Italy, 20133|
|Azienda Ospedaliera Ospedale Niguarda Ca' Granda||Recruiting|
|Milano, Italy, 20162|
|Azienda Ospedaliera Universitaria di Padova||Recruiting|
|Padova, Italy, 35128|
|Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT)||Recruiting|
|Palermo, Italy, 90133|
|Policlinico Tor Vergata||Recruiting|
|Roma, Italy, 00133|
|Ospedale "Lazzaro Spallanzani"||Recruiting|
|Roma, Italy, 00149|
|Ospedale Umberto Iº Policlinico di Roma||Recruiting|
|Roma, Italy, 00161|
|Ospedale Universitario Molinette S. Giovanni Battista di Torino||Recruiting|
|Torino, Italy, 10126|
|Principal Investigator:||Vincenzo Mazzaferro, MD||Istituto Nazionale Tumori, Milano|