NCT05879328

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
12

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Dec 2022

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 23, 2022

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

March 24, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

May 30, 2023

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

May 30, 2023

Status Verified

May 1, 2023

Enrollment Period

2 years

First QC Date

March 24, 2023

Last Update Submit

May 25, 2023

Conditions

Hepatocellular Carcinoma

Keywords

Liver transplantationImmune checkpoint inhibitorsDownstaging

Outcome Measures

Primary Outcomes (1)

  • Recurrence-free survival (RFS)

    Recurrence-free survival (RFS) is defined as the interval (in months) between the date of transplantation and the date on which tumor recurrence is detected at any site at contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) scan, calculated in the entire collected patient population with censoring at the date of death or last follow-up in recurrence-free patients

    up to 2 years

Secondary Outcomes (5)

  • Tumor response

    From the time of signature of informed consent until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 48 months

  • Complication rate

    monthly, up to 2 years

  • Overall survival (OS)

    up to 2 years

  • Patients' reported outcomes (PROs)

    every 3 months for the first six months, then every 6 months up to 2 years

  • Comparison with historical series

    up to 2 years

Interventions

Liver TransplantationPROCEDURE

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.

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

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).

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

RECRUITING

Related Publications (6)

  • Mazzaferro 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.

    PMID: 32615109BACKGROUND

  • Reig M, Forner A, Rimola J, Ferrer-Fabrega J, Burrel M, Garcia-Criado A, Kelley RK, Galle PR, Mazzaferro V, Salem R, Sangro B, Singal AG, Vogel A, Fuster J, Ayuso C, Bruix J. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022 Mar;76(3):681-693. doi: 10.1016/j.jhep.2021.11.018. Epub 2021 Nov 19.

    PMID: 34801630BACKGROUND

  • Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, Pikarsky E, Zhu AX, Finn RS. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022 Mar;19(3):151-172. doi: 10.1038/s41571-021-00573-2. Epub 2021 Nov 11.

    PMID: 34764464BACKGROUND

  • Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

    PMID: 32402160BACKGROUND

  • Mazzaferro V, Sposito C, Zhou J, Pinna AD, De Carlis L, Fan J, Cescon M, Di Sandro S, Yi-Feng H, Lauterio A, Bongini M, Cucchetti A. Metroticket 2.0 Model for Analysis of Competing Risks of Death After Liver Transplantation for Hepatocellular Carcinoma. Gastroenterology. 2018 Jan;154(1):128-139. doi: 10.1053/j.gastro.2017.09.025. Epub 2017 Oct 5.

    PMID: 28989060BACKGROUND

  • Hack SP, Spahn J, Chen M, Cheng AL, Kaseb A, Kudo M, Lee HC, Yopp A, Chow P, Qin S. IMbrave 050: a Phase III trial of atezolizumab plus bevacizumab in high-risk hepatocellular carcinoma after curative resection or ablation. Future Oncol. 2020 May;16(15):975-989. doi: 10.2217/fon-2020-0162. Epub 2020 Apr 30.

    PMID: 32352320BACKGROUND

Related Links

Biospecimen

Retention: SAMPLES WITHOUT DNA

Immune profiling is performed (on day of transplantation, 3, 7, 15, 30, 90 days after transplantation with additional sampling at 6 months) by high resolution flow cytometry (Cytoflex platform) quantifying T cell effector and memory cell subsets (CD3, CD4 and others), T cell subsets associated with response to immunotherapy (PD1, CD28 and others), T reg cell subsets and myeloid cell subsets. Specific antiviral (HCV, HBV, EBV and CMV) and anti-tumor (HCC antigen pool including NY-Eso1, AFP and others) T cell activity is analyzed through ex-vivo peptide stimulation and specific IFNg release detected by Elispot. Immunomodulating and inflammatory cyto- and chemokines levels are quantified through secretome analysis (Cytokine Bead-Array o Fireplex). PBMC and plasma biobanking is performed as backup and for subsequent functional analysis (miRNA profiling,TCR repertoire and Rnaseq of blood immune cell subsets).

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Liver Transplantation

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Tissue TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsDigestive System Surgical ProceduresSurgical Procedures, OperativeOrgan TransplantationTransplantation

Study Officials

  • Vincenzo Mazzaferro, MD, PhD

    Fondazione Istituto Nazionale Tumori Milano - Italy

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Sherrie Bhoori, MD

CONTACT

+39022390sherrie.bhoori@istitutotumori.mi.it

Valentina Bellia, MD

CONTACT

+39022390valentina.bellia@istitutotumori.mi.it

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, MD, PhD

Study Record Dates

First Submitted

March 24, 2023

First Posted

May 30, 2023

Study Start

December 23, 2022

Primary Completion

December 31, 2024

Study Completion

December 31, 2024

Last Updated

May 30, 2023

Record last verified: 2023-05

Locations

IT(1)