A Study of Atezolizumab (Tecentriq) in Combination With Bevacizumab to Investigate Safety and Efficacy in Patients With Unresectable Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy-Amethista (AMETHISTA)

A Phase IIIB, Single Arm, Multicenter Study of Atezolizumab (Tecentriq) in Combination With Bevacizumab to Investigate Safety and Efficacy in Patients With Unresectable Hepatocellular Carcinoma Not Previously Treated With Systemic Therapy-Amethista

This is a Phase IIIb, one arm, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab + bevacizumab in patients with unresectable HCC who have received no prior systemic treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Atezolizumab; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Campania
    • Napoli, Campania, Italy, 80100
      • Fondazione Pascale; U.O. Sperimentazioni Cliniche
    • Napoli, Campania, Italy, 80131
      • Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
    • Napoli, Campania, Italy, 80147
      • Ospedale del Mare; UOC di Oncologia
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O. S. Orsola Malpighi; Ambulatorio Epatocarcinoma (Bolondi)
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
      • Arcispedale Santa Maria Nuova; Oncologia
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
    • Roma, Lazio, Italy, 151
      • Azienda Ospedaliera San Camillo Forlanini
  • Liguria
    • Genova, Liguria, Italy, 16132
      • A.O. Universitaria S. Martino Di Genova
  • Lombardia
    • Bergamo, Lombardia, Italy, 24128
      • Ospedali Riuniti - Bergamo; Gastroenterologia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
    • Milano, Lombardia, Italy, 20133
      • Istituto Nazionale Dei Tumori; Dipartimento Chirurgia Generale - Unita' Trapianti Fegato
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
  • Piemonte
    • Torino, Piemonte, Italy, 10128
      • Azienda Ospedaliera Ordine Mauriziano di Torino
  • Puglia
    • San Giovanni Rotondo, Puglia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
  • Sardegna
    • Cagliari, Sardegna, Italy, 09100
      • A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi
    • Palermo, Sicilia, Italy, 90100
      • A.O.U. Policlinico Paolo Giaccone; Gastroenterologia ed Epatologia
  • Toscana
    • Florence, Toscana, Italy, 50124
      • A.O.U Careggi
    • Pisa, Toscana, Italy, 56100
      • Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2
    • Torrette, Toscana, Italy, 60020
      • Clinica Oncologica-Ospedali Riuniti Ancona
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Unresectable HCC with diagnosis confirmed by histology, with a biopsy within 6 months from recruitment;
• 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 for HCC;
• At least one measurable untreated lesion;
• Patients who received prior local therapy 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;
• ECOG Performance Status of 0 or 1 within 7 days prior to recruitment;
• Child-Pugh class A within 7 days prior to recruitment;
• Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed. In case of varices at high risk of bleeding (corresponding to medium (F2) or large (F3) varices, or F1 varices with cherry red spots or red wale marking) prophylatic treatment per local standard of care must be adopted prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure provided they had no varices at high risk of bleeding;
• Adequate hematologic and end-organ function
• Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade <= 1 prior to study entry, with the exception of alopecia
• Negative HIV test at screening with the following exception: patients with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥200µL, and have an undetectable viral load;
• In patients with viral HCC, documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test;
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.

Exclusion Criteria:

• History of leptomeningeal disease or brain metastases;
• 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 active tuberculosis;
• Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina;
• History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death;
• Prior allogeneic stem cell or solid organ transplantation;
• Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of atezolizumab and 6 months after the last dose of bevacizumab;
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC;
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding;
• A prior bleeding event due to oesophageal and/or gastric varices within 6 months prior to initiation of study treatment;
• Clinically evident ascites;
• Co-infection of HBV and HCV;
• Co-infection with HBV and hepatitis D viral infection;
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures;
• Clinically significant uncontrolled or symptomatic hypercalcemia;
• Inadequately controlled arterial hypertension;
• Significant vascular disease within 6 months prior to initiation of study treatment;
• History of haemoptysis;
• Evidence of bleeding diathesis or significant coagulopathy;
• History of gastrointestinal (GI) fistula, GI perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment;
• History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding prior to initiation of study treatment;
• Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses of large volume;
• Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab + Bevacizumab; Participants will receive atezolizumab 1200 mg intravenous (IV) infusions Q3W (dosed in 3-week cycles) + bevacizumab 15 mg/kg IV Q3W (dosed in 3-week cycles)	Drug: Atezolizumab; Atezolizumab 1200 mg IV infusion q3w; Other Names: Tecentriq; Drug: Bevacizumab; Bevacizumab 15 mg/kg IV Q3W; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Grade 3-5 NCI CTCAE v.5 Bleeding/Haemorrhage	Up to approximately 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival (OS) is defined as the time from initiation of study treatment to death from any cause.	Up to approximately 48 months
Number of Participants with Adverse Events	Number of participants with adverse events with severity determined according to NCI CTCAE v5.0.	Up to approximately 48 months
Progression-Free Survival (PFS)	Progression-free survival (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	Up to approximately 48 months
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as a complete or partial response, as determined by the investigator according to RECIST v1.1	Up to approximately 48 months
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	Up to approximately 48 months
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	Up to approximately 48 months
Post-Progression Survival (PPS)	Post-progression survival (PPS) is defined as the time from the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 to death from any cause.	Up to approximately 48 months
Number of Participants Starting Second or Further Lines of Treatment		Up to approximately 48 months
Number of Participants Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire	Participant self-reported symptomatic Adverse Events (AEs) using National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire.	Up to approximately 48 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Estimated): August 13, 2024
• Study Completion (Estimated): August 13, 2024

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 27, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Bevacizumab; Atezolizumab
• Other Study ID Numbers: ML42243

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No