Hepatocarcinoma Recurrence on the Liver Study - Part2 (HERCOLES2)

August 9, 2019 updated by: Fabrizio Romano, University of Milano Bicocca
Rationale for the trial. To evaluate the impact of surgery on hepatocarcinoma recurrence. Thus, to evaluate the impact of different clinical, radiological, histopathological variables on recurrence after surgical treatment. The nature of this study will allow to observe, over time, the distribution of the considered collection variables, allowing a strictly observational monitoring of possible associations able to suggest models or interpretations, which can then be the basis for the construction of prospective and randomized studies.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Hepatocellular carcinoma (HCC) is 1 of the 5 most common malignancies worldwide and the third most common cause of cancer related mortality of 500,000 deaths globally every year. Although more common in East Asia, the incidence of HCC is increasing in the Western world. Hepatic resection is the first-line therapeutic option and it is accepted as a safe treatment with a proven impact on prognosis, with a low operative mortality as the result of advances in surgical techniques and perioperative management. Nevertheless, surgical resection is applicable in only about 20% to 30% of patients with HCC, since most have poor hepatic reserve function caused by underlying chronic liver disease and multifocal hepatic distributions of HCC.

Although hepatic resection is one of the curative treatments for hepatocellular carcinoma, the recurrence rate of HCC even after curative resection is quite high, estimated to be approximately 50 % during the first 3 years and more than 70 % during the first 5 years after curative resection, and so the postoperative long term results remain unsatisfactory. In this scenario the role of liver transplantation has been, in the last years, predominant, due to the ability of transplant to reduce disease recurrence, because of the treatment of liver cirrhosis associate to HCC which represent the most important driver to recurrence. Otherwise the scarcity of organ source has been a boost to the spread of liver resection, not only confined in the boundary taken into account in the BCLC algorithm (guidelines endorsed by EASL and AASLD), but even in patients considered not suitable for curative treatment as well as liver resection.

Although surgical treatment has been adopted in the last years in more patients outside the Guidelines with satisfactory results in term of mortality, morbidity and Short term oncological outcomes, the limits of this approach remain the long term disease free survival.

Risk factor for recurrence has been yet identified in the last years as hcc dimension, grading, microvascular invasion and satellitosis. The evidence that these two prognostic factors could negatively impact on the long term prognosis enhancing the risk of recurrence, has led many Author to propose anatomical resection (segmental resection) as the ideal surgical treatment to reduce these risks in HCC patients. Otherwise literature results are in conflict regarding the real benefit of this approach. In fact in many patients with HCC and underlying cirrhosis the anatomical approach is not feasible due to the risk of postoperative liver failure. So a parenchyma-sparing technique has been developed and compared to anatomical resection in term of oncological outcomes. Even if radiological and clinical pictures seems to predict the prognosis of resected HCC, the pathophysiology behind the recurrence is still unclear.Currently, data suggests two type of recurrence presentation: intrahepatic metastasization (IM) and multicentric occurrence (MO) of de novo HCC based on the precancerous status of the remnant diseased liver. Several effort has been done to preoperatively identified the 2 pattern of recurrences. Genetical studied has been performed, especially in eastern countries to better clarify and understand the impact of the 2 phenomena. In the japanese guidelines are described histo-pathological hallmarks able, in retrospect, to define the type of recurrence, metastases or de novo tumor. Moreover, several recent studies including a metanalysis, seems to show that de novo recurrence could have a better prognosis when approached surgically, with a significant improvement in overall and disease-free survival rates. The model of HCC recurrence is not yet well clarified as well as the best treatment of hcc recurrence. On these data is based the proposal to create an Italian study project on surgical treatment and surgical outcomes of hepatocellular carcinoma in term of disease free survival. The idea growth up from the finding that, although the curative intent of surgical approach, results are not so satisfactory and it seems to not ameliorate the long term patient's prognosis and long term disease-free outcome without the need for therapies, conditioning the real everyday life of patient. In Italy is not yet present a study group that draw together the experience of surgical centers with low,medium or high volume of surgical procedures on HCC, with the intent to offer radical cure through surgery as the first choice treatment. The intent is to collect Big Data through a common database, with high power of analysis and high scientific impact, to better understand the mechanism which regulate HCC recurrence and to identify the best clinical treatment option for these patients.

Study Type

Observational

Enrollment (Anticipated)

3000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Bari, Italy
        • Chirurgia Rubino - Policlinico di Bari
        • Contact:
        • Principal Investigator:
          • Riccardo Memeo, MD
      • Bologna, Italy
        • Ospedale Maggiore- AUSL
        • Contact:
        • Principal Investigator:
          • Elio Jovine, Prof
        • Sub-Investigator:
          • Matteo Zanello, MD
      • Bolzano, Italy
        • Chirurgia Generale Bolzano
        • Contact:
        • Principal Investigator:
          • Antonio Frena, MD
      • Brescia, Italy
        • Spedali Civili
        • Contact:
        • Principal Investigator:
          • Gianluca Baiocchi, MD, PhD
      • Brescia, Italy
      • Forlì, Italy
        • Chirurgia Generale Ospedale Pierantoni - Morgagni
        • Contact:
        • Principal Investigator:
          • Giorgio Ercolani, MD
      • Lecco, Italy
        • Ospedale A. Manzoni - ASST Lecco
        • Contact:
        • Principal Investigator:
          • Marco Chiarelli, MD
      • Mantova, Italy
        • ASST-Mantova
        • Contact:
        • Principal Investigator:
          • Luigi Boccia, MD
        • Sub-Investigator:
          • Michela De Angelis, MD
      • Milan, Italy
        • Asst-Fbf-Sacco Polo Universitario H. Sacco Chirurgia 2
        • Contact:
        • Principal Investigator:
          • Michele Crespi, MD
      • Milan, Italy
        • IRCCS Osp. San Raffaele, Divisione Chirurgia Generale Epatobiliare
        • Contact:
        • Principal Investigator:
          • Luca Aldrighetti, MD
      • Monza, Italy
      • Parma, Italy
        • UOS Chirurgia Oncologica ad inidirzzo epato-bilio-pancreatico
        • Contact:
        • Sub-Investigator:
          • Maurizio Iaria, MD
        • Principal Investigator:
          • Raffaele Dalla Valle, MD
      • Pavia, Italy
        • Fondazione IRCCS Policlinico San Matteo
        • Contact:
        • Principal Investigator:
          • Marcello Maestri, MD, PhD
        • Sub-Investigator:
          • Tommaso Dominioni, MD
      • Rome, Italy
        • Fondazione Policlinico Universitario A. Gemelli, IRCCS
        • Contact:
        • Principal Investigator:
          • Felice Giuliante, Prof
        • Sub-Investigator:
          • Francesco Ardito, Prof
      • Rome, Italy
        • IRCCS Istituto Nazionale Tumori Regina Elena
        • Contact:
        • Principal Investigator:
          • Gianluca Grazi, MD
        • Sub-Investigator:
          • Valerio De Peppo, MD
      • Rozzano, Italy
        • Humanitas Research Hospital
        • Principal Investigator:
          • Guido Torzilli, MD, PhD
        • Contact:
        • Sub-Investigator:
          • Matteo Donadon, MD, PhD
      • Savona, Italy
        • Ospedale San Paolo
        • Contact:
        • Principal Investigator:
          • Guido Griseri, MD
        • Sub-Investigator:
          • Cecilia Ferrari, MD
      • Treviso, Italy
      • Verona, Italy
        • Chirurgia Epatobiliare Università degli studi di Verona
        • Contact:
        • Principal Investigator:
          • Andrea Ruzzenente, MD
        • Sub-Investigator:
          • Simone Conci, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

All consecutive patients treated by surgery for HCC

Description

Inclusion Criteria:

  • No age limit.
  • Hepatocarcinoma diagnosis confirmed at histological specimen
  • Every single patients with first HCC diagnosis or with a recurrence/persistence disease evaluated and treated with surgery at the participating center.
  • the assessment for patient enrollment must have been performed starting from 02/02/2019.

Exclusion Criteria:

  • Surgery as a downstaging therapy for transplant
  • Patients treated with surgery in case of not-curative intent (palliation, best supportive care, etc).
  • Histopathological specimen of combined liver primary neoplasms (e.g. "hepatocholangiocarcinoma'').
  • Patients with other tumors in the previous past.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free-Survival
Time Frame: 15 years of follow-up
Disease Free Survival: the time between surgery and event of recurrence or death measured in months. If no event, patients will be censored at the last available follow-up date.
15 years of follow-up
Overall Survival
Time Frame: 15 years of follow-up
The time from surgery to death measured in months. If no event, patients will be censored at the last available follow-up.
15 years of follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Localization of the recurrence
Time Frame: 15 years of follow-up
Presence of relapse disease on the surgical cut surface rather than at distance
15 years of follow-up
Number of redo-surgery
Time Frame: 15 years
Number of patients who experienced a recurrence after first surgery and has been submitted to a redo-surgery procedure
15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Milano Bicocca

Investigators

  • Principal Investigator: Fabrizio Romano, MD, University of Milan-Bicocca
  • Principal Investigator: Simone Famularo, MD, University of Milan Bicocca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2019

Primary Completion (Anticipated)

September 1, 2022

Study Completion (Anticipated)

May 1, 2034

Study Registration Dates

First Submitted

July 6, 2019

First Submitted That Met QC Criteria

August 9, 2019

First Posted (Actual)

August 12, 2019

Study Record Updates

Last Update Posted (Actual)

August 12, 2019

Last Update Submitted That Met QC Criteria

August 9, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HERCOLES-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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