Trial Title:
The ImmunoXXL Study
NCT ID:
NCT05879328
Condition:
Hepatocellular Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Conditions: Keywords:
Liver transplantation
Immune checkpoint inhibitors
Downstaging
Study type:
Observational
Overall status:
Recruiting
Study design:
Time perspective:
Prospective
Intervention:
Intervention type:
Procedure
Intervention name:
Liver Transplantation
Description:
Liver transplantation (LT) is an accepted surgical therapy for hepatocellular carcinoma
(HCC) in patients who achieve effective and sustained tumor downstaging; in this study
liver transplantation will be performed in patients undergoing a successful
hepatocellular carcinoma (HCC) downstaging with the combination of atezolizumab and
bevacizumab.
Summary:
This study is aimed at confirming data of efficacy and safety of liver transplantation
(LT) in patients with hepatocellular carcinoma (HCC) beyond current transplant criteria
who demonstrate a sustained partial or complete radiological response to the atezolizumab
and bevacizumab combination treatment, prescribed after completion of loco-regional
therapies or as a first line systemic treatment.
The aim of the study is to demonstrate that liver transplantation, after effective HCC
downstaging with atezolizumab and bevacizumab combination, may confer a survival benefit
over atezolizumab and bevacizumab maintained treatment alone and that this strategy
(tested in a consecutive non-randomized cohort) is not undermined by added risks.
Detailed description:
Liver transplantation (LT) is an accepted treatment for hepatocellular carcinoma (HCC).
For patients with intermediate-advanced stage hepatocellular carcinoma (HCC) otherwise
not eligible to curative treatments, tumor downstaging to LT is now an accepted strategy,
as transplantation after a successful downstaging with loco-regional treatments confers a
significant benefit in survival and recurrence/progression free survival compared to
non-transplant strategies. Immune checkpoint inhibitors (ICIs) efficacy has been proven
both as an adjuvant treatment in surgically treated HCCs and as a first line systemic
therapy for advanced stage patients; in both cases with more than tolerable safety
profiles. Therefore there is interest in using immunotherapy as a downstaging treatment
prior to curative liver transplantation (LT).
This observational prospective single-arm study enrols patients on the transplant list
after the achievement of a sustained radiological partial response (PR) or complete
response (CR) on treatment with atezolizumab (flat dose of 1200 mg) and bevacizumab (15
mg/Kg) given intravenously every three weeks for a non otherwise treatable
intermediate-advanced HCC.
Radiological response has to be sustained (for at least 3 months) and accompanied by a
level of alpha fetoprotein (AFP) ≤ 100 UI/ml, if levels > 100 UI/ml at baseline or by
decrease of the level of AFP parallel to the modified response evaluation criteria in
solid tumors (mRECIST), if baseline levels ≤ 100 UI/ml.
Radiological and biochemical responses need to satisfy a ≥60% post-transplant survival at
5 years according to the Metroticket 2.0 calculator (www.hcc-olt-metroticket.org).
While on the liver transplant waiting list, treatment with atezolizumab and bevacizumab
will be stopped. Treatment may be restored, according to clinical judgement:
- if waiting time on transplant list > 2 months
- if radiological and/or AFP progression within transplant criteria (predicted 5 year
survival according to Metroticket 2.0 calculator ≥60%).
- if radiological and/or AFP progression beyond transplant criteria (predicted 5 year
survival according to Metroticket 2.0 calculator < 60%); patients will be delisted
(drop out) and treated according to clinical judgement and local standards.
Priority on the waiting list will follow local standards for candidates with HCC at risk
of progression. Both donation after brain death (DBD) and after cardiac death (DCD) will
be accepted for organ procurement.
Participants will also undergo a comprehensive blood immunomonitoring in order to explore
the effect of liver transplantation and of related immunosuppressive regimens on the
anti-tumoral immunomediated environment induced by the combination of atezolizumab and
bevacizumab.
Criteria for eligibility:
Study pop:
Intermediate-advanced HCC patients achieving complete response (CR) or partial response
(PR) on treatment with atezolizumab and bevacizumab (approved dosages).
Radiological response has to be sustained (for at least 3 months) and accompanied by a
level of alpha fetoprotein (AFP) ≤ 100 UI/ml if levels > 100 UI/ml at baseline or by
decrease of the level of AFP parallel to the mRECIST response, if baseline levels >100
UI/ml, to confirm a partial response (PR).
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
- age ≥ 18 and < 75 years
- signed Informed Consent Form
- hepatocellular carcinoma (HCC) previously diagnosed by histology/cytology or
clinically by the American Association for the Study of Liver Disease (AASLD)
criteria in cirrhotic patients. Patients without cirrhosis require compulsory
histological confirmation of diagnosis.
- hepatocellular carcinoma (HCC) at diagnosis beyond "AFP-adjusted up-to-seven
criteria" not amenable to loco-regional treatments and with sustained (at least 3
months) complete o partial response according to mRECIST after systemic treatment
with atezolizumab and bevacizumab
- no major contraindications (cardiological, pulmonary, mental and social) to
transplantation.
Exclusion Criteria:
- presence of extra-hepatic spread (EHS) defined as organ involvement other than the
liver and hilar lymphnodes with short axis > 2 cm
- presence of tumoral portal vein thrombosis invading the main portal trunk for more
than 1 cm in cranio-caudal extension (measured at coronal reconstructions scans at
contrast enhanced CT/MRI).
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fondazione IRCCS Istituto Nazionale dei Tumori
Address:
City:
Milano
Zip:
20133
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Vincenzo Mazzaferro, MD, PhD
Phone:
+39 02 2390
Phone ext:
2760
Email:
vincenzo.mazzaferro@istitutotumori.mi.it
Contact backup:
Last name:
Sherrie Bhoori, MD
Phone:
+39 02 23902338
Phone ext:
3474
Email:
sherrie.bhoori@istitutotumori.mi.it
Investigator:
Last name:
Vincenzo Mazzaferro, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Sherrie Bhoori, MD
Email:
Principal Investigator
Investigator:
Last name:
Valentina Bellia, MD
Email:
Sub-Investigator
Investigator:
Last name:
Carlo Sposito, MD
Email:
Sub-Investigator
Investigator:
Last name:
Marco Bongini, MD
Email:
Sub-Investigator
Investigator:
Last name:
Licia Rivoltini, MD
Email:
Sub-Investigator
Investigator:
Last name:
Nicola Cerioli, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Michela Dosi, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Francesca Rini, Lab Tech
Email:
Sub-Investigator
Investigator:
Last name:
Agata Cova, Lab Tech
Email:
Sub-Investigator
Investigator:
Last name:
Paola Squarcina, Lab Tech
Email:
Sub-Investigator
Investigator:
Last name:
Marta Vaiani, MD
Email:
Sub-Investigator
Investigator:
Last name:
Giuseppe Leoncini, MD
Email:
Sub-Investigator
Investigator:
Last name:
Monica Niger, MD
Email:
Sub-Investigator
Investigator:
Last name:
Federico Nicchetti, MD
Email:
Sub-Investigator
Start date:
December 23, 2022
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Agency class:
Other
Source:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05879328
http://www.hcc-olt-metroticket.org/
