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AMETHISTA: 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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04487067
Collaborator
(none)
152
Enrollment
21
Locations
1
Arm
35.2
Anticipated Duration (Months)
7.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
152 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Aug 25, 2020
Anticipated Primary Completion Date :
Jul 31, 2023
Anticipated Study Completion Date :
Jul 31, 2023

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Grade 3-5 NCI CTCAE v.5 Bleeding/Haemorrhage [Up to approximately 48 months]

    Secondary Outcome Measures

    1. Overall Survival (OS) [Up to approximately 48 months]

      Overall survival (OS) is defined as the time from initiation of study treatment to death from any cause.

    2. Number of Participants with Adverse Events [Up to approximately 48 months]

      Number of participants with adverse events with severity determined according to NCI CTCAE v5.0.

    3. Progression-Free Survival (PFS) [Up to approximately 48 months]

      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

    4. Objective Response Rate (ORR) [Up to approximately 48 months]

      Objective response rate (ORR) is defined as a complete or partial response, as determined by the investigator according to RECIST v1.1

    5. Time to Progression (TTP) [Up to approximately 48 months]

      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

    6. Duration of Response (DOR) [Up to approximately 48 months]

      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

    7. Post-Progression Survival (PPS) [Up to approximately 48 months]

      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.

    8. Number of Participants Starting Second or Further Lines of Treatment [Up to approximately 48 months]

    9. Number of Participants Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire [Up to approximately 48 months]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fondazione Pascale; U.O. Sperimentazioni Cliniche Napoli Campania Italy 80100
    2 Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica Napoli Campania Italy 80131
    3 Ospedale del Mare; UOC di Oncologia Napoli Campania Italy 80147
    4 A.O. S. Orsola Malpighi; Ambulatorio Epatocarcinoma (Bolondi) Bologna Emilia-Romagna Italy 40138
    5 Arcispedale Santa Maria Nuova; Oncologia Reggio Emilia Emilia-Romagna Italy 42100
    6 Azienda Ospedaliera San Camillo Forlanini Roma Lazio Italy 00152
    7 Policlinico Universitario Agostino Gemelli Roma Lazio Italy 00168
    8 A.O. Universitaria S. Martino Di Genova Genova Liguria Italy 16132
    9 Ospedali Riuniti - Bergamo; Gastroenterologia Bergamo Lombardia Italy 24128
    10 Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia Milano Lombardia Italy 20122
    11 Istituto Nazionale Dei Tumori; Dipartimento Chirurgia Generale - Unita' Trapianti Fegato Milano Lombardia Italy 20133
    12 Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia Rozzano Lombardia Italy 20089
    13 Azienda Ospedaliera Ordine Mauriziano di Torino Torino Piemonte Italy 10128
    14 IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia San Giovanni Rotondo Puglia Italy 71013
    15 A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia Cagliari Sardegna Italy 09100
    16 A.O.U. Policlinico Paolo Giaccone; Gastroenterologia ed Epatologia Palermo Sicilia Italy 90127
    17 Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi Palermo Sicilia Italy 90127
    18 A.O.U Careggi Florence Toscana Italy 50124
    19 Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2 Pisa Toscana Italy 56100
    20 Clinica Oncologica-Ospedali Riuniti Ancona Torrette Toscana Italy 60020
    21 IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II Padova Veneto Italy 35128

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04487067
    Other Study ID Numbers:
    • ML42243
    First Posted:
    Jul 27, 2020
    Last Update Posted:
    Jun 15, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Hepatocellular
    Bevacizumab
    Atezolizumab

    Study Results

    No Results Posted as of Jun 15, 2022