An interventional study of Liver transplantation in Carcinoma, Hepatocellular and Cirrhosis, sponsored by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano. Completed at 10 sites in Italy. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2021-10-11.
Sponsored by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano · Not applicable, Interventional, and Treatment
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.
Downstaging phase
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.
Bridging phase
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.
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).
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 74 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →Fondazione IRCCS Istituto Nazionale dei Tumori, Milano is the lead sponsor of 169 studies on the registry; 48 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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
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
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
For Phase II - Time to Tumoral Event (TTE)
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.
Time frame: Every 4 months
For Phase III - Overall Survival
Time form the date of randomization and the date of death, with censoring at the date of last contact for event-free patients
Time frame: Every 4 months
Transplant vs. non transplant strategy cost-benefit analysis
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
Time frame: Approx. 1 year after the last patient randomized
Validation of modified RECIST criteria of radiological response to downstaging treatments
Radiology/pathology correlation on efficacy of downstaging treatments in achieving tumor response, as a basis for possible validation of modified RECIST criteria.
Time frame: Approx. 8 months after the last patient randomized
Validation of the Metroticket model for the prognosis of survival after liver transplantation in patients exceeding Milan Criteria
http://www.hcc-olt-metroticket.org/
Time frame: Approx. 1 year after the last patient randomized
This study is completed, as verified in Oct 2021. You cannot join it, but the record below documents what was studied.
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Fondazione IRCCS Istituto Nazionale dei Tumori, Milano