Clinical trial NCT04487067: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-07-27
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Grade 3-5 NCI CTCAE v.5 Bleeding/Haemorrhage
timeFrame: Up to approximately 48 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 48 months
measure: Number of Participants with Adverse Events
timeFrame: Up to approximately 48 months
measure: Progression-Free Survival (PFS)
timeFrame: Up to approximately 48 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 48 months
measure: Time to Progression (TTP)
timeFrame: Up to approximately 48 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 48 months
measure: Post-Progression Survival (PPS)
timeFrame: Up to approximately 48 months
measure: Number of Participants Starting Second or Further Lines of Treatment
timeFrame: Up to approximately 48 months
measure: Number of Participants Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire
timeFrame: Up to approximately 48 months
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Fondazione Pascale; U.O. Sperimentazioni Cliniche
state: Campania
city: Napoli
country: Italy
facility: Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
state: Campania
city: Napoli
country: Italy
facility: Ospedale del Mare; UOC di Oncologia
state: Campania
city: Bologna
country: Italy
facility: A.O. S. Orsola Malpighi; Ambulatorio Epatocarcinoma (Bolondi)
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova; Oncologia
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
state: Lazio
city: Genova
country: Italy
facility: A.O. Universitaria S. Martino Di Genova
state: Liguria
city: Bergamo
country: Italy
facility: Ospedali Riuniti - Bergamo; Gastroenterologia
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
state: Lombardia
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori; Dipartimento Chirurgia Generale - Unita' Trapianti Fegato
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano di Torino
state: Piemonte
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
state: Puglia
city: Cagliari
country: Italy
facility: A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia
state: Sardegna
city: Palermo
country: Italy
facility: A.O.U. Policlinico Paolo Giaccone; Gastroenterologia ed Epatologia
state: Sicilia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Di Rilievo Nazionale E Di Alta Specializzazione Garibaldi
state: Sicilia
city: Florence
country: Italy
facility: A.O.U Careggi
state: Toscana
city: Pisa
country: Italy
facility: Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2
state: Toscana
city: Torrette
country: Italy
facility: Clinica Oncologica-Ospedali Riuniti Ancona
state: Toscana
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
state: Veneto
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: