A Study of Atezolizumab in Combination With Bevacizumab in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

Carcinoma, Hepatocellular Clinical Trial

Official title:

A Phase IIIb, Single Arm, Multicenter Study of Atezolizumab in Combination With Bevacizumab to Investigate Safety and Efficacy in Spanish Patients With Unresectable or Unsuitable for Locoregional Treatments Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04732286
• Other study ID #: ML42600
• Status: Completed
• Phase: Phase 3
• Start date: May 4, 2021
• Est. completion date: April 26, 2024

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase IIIb, one arm, multicenter, open-label study primarily designed to evaluate the safety of atezolizumab + bevacizumab in participants with unresectable or unsuitable for locoregional treatments for metastatic HCC not previously treated with systemic therapy. As part of its secondary objectives, this study is also designed to evaluate the efficacy of atezolizumab and bevacizumab in these participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: April 26, 2024
• Est. primary completion date: April 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology or radiologically, following the AASLD criteria

• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies

• No prior systemic therapy (including systemic investigational agents) for HCC

• At least one measurable (per RECIST 1.1) untreated lesion detected by CT scan

• Patients who received prior local therapy such as radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization (excluding transarterial radioembolization.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1

Exclusion Criteria:

• Active or history of autoimmune disease or immune deficiency

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC

• Co-infection of HBV and HCV

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered intravenously at a dose of 1200 mg on Day 1 of each 21-day cycle.
• Bevacizumab
Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Spain	Hospital General Univ. de Alicante; Servicio de Hepatologia	Alicante
Spain	Complejo Hospitalario Torrecardenas; Servicio de Hepatologia	Almeria
Spain	Hospital Clinic i Provincial; Servicio de Hepatología	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hepatologia	Barcelona
Spain	Hospital de Basurto; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Hepatologia	Cordoba
Spain	Hospital General Universitario de Elche; Servicio de Oncologia	Elche	Alicante
Spain	Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia	Jaen
Spain	Hospital de Gran Canaria Dr. Negrin; Servicio de Aparato Digestivo	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Lucus Augusti; Servicio de Oncologia	Lugo
Spain	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Aparato Digestivo	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Ramón y Cajal; Servicio de Digestivo	Madrid
Spain	Hospital Univ. Central de Asturias; servicio de Digestivo	Oviedo	Asturias
Spain	Hospital Son Llatzer; Servicio de Oncologia	Palma de Mallorca	Islas Baleares
Spain	Clinica Universitaria de Navarra; Servicio de Hepatologia	Pamplona/iruña	Navarra
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Hepatologia	Sabadell	Barcelona
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Univ. Nuestra Señora de Valme; Servicio de Oncologia	Sevilla
Spain	Hospital Universitario de Torrejon; Servicio de Oncología	Torrejón de Ardoz	Madrid
Spain	Hospital Universitari i Politecnic La Fe; Oncologia	Valencia
Spain	Hospital Universitario Miguel Servet; Servicio Oncologia	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Discontinuations of Atezolizumab and/or Bevacizumab Due to Adverse Events of Grade = 3		Initiation fo study treatment up to approximately 3 years
Secondary	Overall Survival (OS)	OS is defined as the time from initiation of study treatment to death from any cause.	Initiation of study treatment to death from any cause (up to approximately 3 years)
Secondary	Severity of Adverse Events According to NCI CTCAE v5.0	The adverse event severity grading scale for the NCI CTCAE (v5.0) will be used for assessing adverse event severity.	Initiation of study treatment up to approximately 3 years
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.	Initiation of study treatment to first occurrence of disease progression or death from any cause (whichever occurs first)(up to approximately 3 years)
Secondary	Time to Progression (TTP)	Time to progression (TTP) is defined as the time from initiation of study treatment to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1 criteria.	Initiation of study treatment to first occurrence of disease progression (up to approximately 3 years)
Secondary	Duration of Response (DOR)	Duration of Response (DOR) is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1.	Documented objective response to disease progression or death from any cause (whichever occurs first)(up to approximately 3 years)
Secondary	Number/Rate of Participants Starting Second Line Treatment		Up to approximately 3 years
Secondary	International Normalized Ratio (INR)		Up to approximately 3 years
Secondary	Presence of Absence of Ascites and/or Hepatic Encephalopathy		Up to approximately 3 years
Secondary	Albumin-Bilirubin (ALBI) Assessment Grades of 1 to 3	Albumin-Bilirubin Assessment Grades of 1 to 3 based on ALBI score calculation.	Up to approximately 3 years