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

Hepatocellular Carcinoma Clinical Trial

— IMMUNOGLYPIC  

Official title:

Evaluation of the Contribution of Glypican-3 as a Pronostic Factor in Patients With Advanced Hepatocellular Carcinoma Treated by Immunotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05263830
• Other study ID #: APHP210978
• Status: Recruiting
• Start date: September 8, 2023
• Est. completion date: September 8, 2027

Study information

• Verified date: September 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Manon ALLAIRE, Dr
• Phone: 0142161034
• Email: manon.allaire[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

When hepatocellular carcinoma (HCC) is diagnosed, only 25% of patients will be able to have a curative treatment such as liver transplantation, treatment by ablation or surgical resection. In the majority of cases, patients will only have access to so-called palliative treatment. For many years, the only treatment available for patients with advanced HCC was sorafenib, a tyrosine kinase inhibitor with an average overall survival of 10.6 months. 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. Indeed, the overall survival (OS) and progression-free survival rates (PFS) were significantly higher in the Atezolizumab+Bevacizumab arm (OS: 67.2% at 12 months and PFS: 6.8 months) versus Sorafenib (OS: 54.6% at 12 months, PFS 4.3 months). The recent approval of the treatment in France is a unique opportunity to carry out a pilot study on clinical, biological, histological, molecular and immune prognostic and predictive factors in patients treated with the Atezolizumab+Bevacizumab combination. Identifying new predictive biomarkers of response is essential to optimize the identification of patients who will benefit from immunotherapy. HCCs are characterized by multiple genomic alterations and the abnormal expression of numerous pro- and anti-oncogenic genes. Glypican-3 (GPC-3) is a cell surface glycoprotein that belongs to the family of heparan sulfate chain proteoglycans. As a co-receptor, GPC-3 is involved in the control of several major signaling pathways (IGF2, Wnt/beta-catenin, etc.) and plays an important role in cell proliferation and tissue growth. At the tumoral level, GPC-3 is directly implicated in several cancers and more particularly in HCC. GPC-3 is overexpressed in 72% of HCCs and its expression is absent in normal liver tissues and benign liver lesions. GPC-3 overexpression is associated with the state of cell tumor differentiation and proliferation in HCC, tumor aggressiveness, as well as poor prognosis and shorter OS. GPC-3 overexpression in serum also 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: September 8, 2027
• Est. primary completion date: September 8, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• 18 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Other:
• Quantitative assay of GlypicanPC-3
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

Locations

Country	Name	City	State
France	Service hépato-gastroentérologie, Hôpital la Pitié-Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Evaluate overall survival		at 24 months
Secondary	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.	Correlation of the values of GPC-3, PIVKA, AFP	at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab
Secondary	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.	Correlation between survival at 24 months and the values of GPC-3, PIVKA, AFP before, 3 weeks and 3 months after the start of treatment and the change in value.	at inclusion, at 3 weeks and at 3 months of the first infusion of Atezolizumab/Bevacizumab, at 24 months
Secondary	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,