Glypican-3 as a Prognostic Factor in Patients With Hepatocellular Carcinoma Treated by Immunotherapy

NCT05263830 | Recruiting

• 1 other identifier: APHP210978
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Recently, the positive results of the Imbrave 150 study (randomized study comparing Atezolizumab+Bevacizumab versus Sorafenib) prompted investigators to redefine their management strategy for advanced HCC by proposing the combination Atezolizumab+ Bevacizumab as first-line treatment in these patients. Identifying new predictive biomarkers of response is essential to optimize the identification of patients who will benefit from immunotherapy. Glypican-3 (GPC-3) is a cell surface glycoprotein that belongs to the family of heparan sulfate chain proteoglycan that is directly implicated in several cancers and more particularly in HCC. GPC-3 overexpression in serum predicts a poor prognosis for patients with HCC and is associated with early tumor recurrence. Through this study, the investigators want to determine whether the concentration of circulating GPC-3 alone, or in combination with other biomarkers used in current practice (PIVKA, AFP) could predict the response to treatment with Atezolizumab/Bevacizumab and OS.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Glypican 3; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• evaluate concentration of circulating GPC-3

  Evaluation of the change in GPC-3 concentration before, at 3 weeks (second infusion) and at 3 months from the first infusion of Atezolizumab/Bevacizumab .

  at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab

Secondary Outcomes (4)

• Evaluate overall survival

  at 24 months

• Evaluation of the combination of circulating GPC-3 level with other biomarkers (PIVKA, AFP) before, 3 weeks and 3 months after initiation of Atezolizumab/Bevacizumab and/or their variation value could predict treatment response.

  at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab

• Evaluation of the combination of circulating GPC-3 level with other biomarkers (PIVKA, AFP) before, 3 weeks and 3 months after initiation of Atezolizumab/Bevacizumab and/or their variation value could predict overall Survival.

  at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab, at 24 months

• Evaluation of the HCC response to treatment on Imaging assessment (CT-scan and MRI) every 3 months according to the miRECIST criteria (combination of mRECIST and iRECIST criteria)

  at inclusion, at 3,6,9,12,15,18,21 and 24 months of the first infusion of Atezolizumab/Bevacizumab,

Study Arms (2)

Patient with hepatocellular carcinoma treated with Atezolizumab / Bevacizumab

Patients with an indication for treatment with Atezolizumab / Bevacizumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting.

Other: Quantitative assay of GlypicanPC-3

Patient with hepatocellular carcinoma treated with Durvalumab/Trémélimumab

Patients with an indication for treatment with Durvalumab/Trémélimumab for the management of an advanced disciplinary hepatocellular carcinoma in a multidisciplinary consultation meeting.

Other: Quantitative assay of GlypicanPC-3

Interventions

Quantitative assay of GlypicanPC-3 OTHER

Quantitative assay of GlypicanPC-3 in human serum is performed by direct sandwich immunoassay ( CanAg Glypican3 EIA - Fujirebio ) on microplate using two mouse monoclonal antibodies against two epitopes of the Glypican-3 core protein

Patient with hepatocellular carcinoma treated with Atezolizumab / Bevacizumab; Patient with hepatocellular carcinoma treated with Durvalumab/Trémélimumab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with an indication for treatment with Atezolizumab/Bevacizumab for advanced HCC at a multidisciplinary consultation meeting

You may qualify if:

• years ≤ age \< 90 years
• Diagnosed with HCC developed on a cirrhotic liver or on chronic liver disease that has not reached the stage of cirrhosis regardless of the etiology diagnosed according to the diagnostic criteria for TNCD updated in June 2021 (1)
• Having an indication for systemic therapy with Atezolizumab+Bevacizumab validated in multidisciplinary meeting according to the current recommendations of cancer societies.
• Understanding the French language.
• Having been informed and accepted to participate to the study.

You may not qualify if:

• HIV or known immune deficiency or immunosuppressive treatment
• Autoimmune diseases or other immunotherapies
• History of portosystemic shunt or liver transplantation
• Sepsis, vasoconstrictor drugs.
• Pregnant or breastfeeding women
• Protected populations: under guardianship or curators

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Service hépato-gastroentérologie, Hôpital la Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Simpson-Golabi-Behmel syndrome

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Manon ALLAIRE, Dr

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manon ALLAIRE, Dr

CONTACT

0142161034; manon.allaire@aphp.fr

Christine BROCHET, Dr

CONTACT

0142162061; christine.brochet@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: March 3, 2022
• Study Start: September 8, 2023
• Primary Completion (Estimated): September 8, 2029
• Study Completion (Estimated): September 8, 2029
• Last Updated: December 16, 2025

Record last verified: 2025-12

Locations

FR (1)